Abstract
Background
Blood flow restriction (BFR) is a process of using inflatable cuffs to create vascular occlusion within a limb during exercise. The technique can stimulate muscle hypertrophy and improve physical function; however, most of these studies have enrolled healthy, young men with a focus on athletic performance. Furthermore, much of the information on BFR comes from studies with small samples sizes, limited follow-up time, and varied research designs resulting in greater design, selection, and sampling bias. Despite these limitations, BFR’s popularity is increasing as a clinical rehabilitation tool for aging patients. It is important for practitioners to have a clear understanding of the reported effects of BFR specifically in older adults while simultaneously critically evaluating the available literature before deciding to employ the technique.
Questions/purposes
(1) Does BFR induce skeletal muscle hypertrophy in adults older than 50 years of age? (2) Does BFR improve muscle strength and/or physical function in adults older than 50 years?
Methods
Using PubMed, Google Scholar, Web of Science, and Science Direct, we conducted a systematic review of articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess the reported effects of BFR on skeletal muscle in older adults. Included articles enrolled participants 50 years of age or older and used BFR in conjunction with exercise to study the effects of BFR on musculoskeletal outcomes and functionality. The following search terms were used: “blood flow restriction” OR “KAATSU” OR “ischemic training” AND “clinical” AND “elderly.” After duplicates were removed, 1574 articles were reviewed for eligibility, and 30 articles were retained with interventions duration ranging from cross-sectional to 16 weeks. Sample sizes ranged from 6 to 56 participants, and exercise tasks included passive mobilization or electrical stimulation; walking; resistance training using machines, free weights, body weight, or elastic bands; and water-based activities. Furthermore, healthy participants and those with cardiovascular disease, osteoarthritis, osteoporosis, sporadic inclusion body myositis, spinal cord injuries, and current coma patients were studied. Lastly, retained articles were assigned a risk of bias score using aspects of the Risk of Bias in Nonrandomized Studies of Interventions and the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials.
Results
BFR, in combination with a variety of exercises, was found to result in muscle hypertrophy as measured by muscle cross-sectional area, thickness, volume, mass, or circumference. Effect sizes for BFR’s ability to induce muscle hypertrophy were calculated for 16 of the 30 papers and averaged 0.75. BFR was also shown to improve muscle strength and functional performance. Effect sizes were calculated for 21 of the 30 papers averaging 1.15.
Conclusions
Available evidence suggests BFR may demonstrate utility in aiding rehabilitation efforts in adults older than 50 years of age, especially for inducing muscle hypertrophy, combating muscle atrophy, increasing muscle strength, and improving muscle function. However, most studies in this systematic review were at moderate or high risk of bias; that being so, the findings in this systematic review should be confirmed, ideally using greater sample sizes, randomization of participants, and extended follow-up durations.
Level of Evidence
Level II, systematic review.
Introduction
Aging patients commonly have muscle atrophy and associated physical decline, which are accelerated after musculoskeletal injury or surgery. In the 1990s, Yoskiaki Sato developed KAATSU training, also known as blood flow restriction (BFR) therapy, to combat muscle atrophy [54]. This technique involves using inflatable cuffs around limbs to create vascular occlusion, thereby altering local interstitial pressures and trapping exercise-induced metabolites. BFR therapy has reported efficacy for improving performance in athletes [2, 48, 63, 64], with growing evidence of benefits in hospitalized patients [38, 65, 74], including older adults [4, 25, 29, 62]. Improvements from BFR have been found when it is used in conjunction with a variety of training modalities, such as walking [3, 4, 48], cycling [1], low-load resistance training [29, 61, 62], and body-weight exercises [26].
Because musculoskeletal injuries often require prolonged healing times, negative downstream disuse effects on bone and muscle may result in chronic detrimental losses in physical function, which is of particular concern to older adults with respect to immobility and resultant physical and mental health decline. As such, cardiovascular, muscular, and skeletal responses to exercise interventions with BFR are of special interest in this large and growing clinical cohort. Of the evidence available, systematic reviews of BFR safety indicate it is not associated with additional cardiovascular stresses or morbidity [10, 23, 36, 50]. Rather, the acute and local elevated blood pressure responses to BFR result in a variety of positive cardiovascular adaptations such as improved vascular endothelial function, peripheral blood circulation [58], and arterial and venous compliance [25, 46]. Plausible mechanisms underlying BFR’s ability to induce muscle hypertrophy and/or protect from muscle atrophy include biochemical responses influencing accelerated muscle hypertrophy [16, 17, 21, 30, 32, 53, 62, 63] and enhanced muscle performance because of oxygen-dependent shifts in fiber type recruitment [63, 65, 66].
Patients at risk of muscle atrophy because of extended periods of immobilization, such as those with prolonged bed rest, unilateral limb unloading, or casting, may be excellent candidates for BFR [12], especially because BFR administered on the contralateral limb may result in positive adaptations in the injured limb [39]. Despite the limited research supporting BFR’s application in adults older than 50 years, BFR usage is increasing as a clinical rehabilitation tool. It is important for clinicians and practitioners to gain a comprehensive understanding of the reported effects of BFR in older adults and the limitations of that research body before using the technique in their clinics.
To address these knowledge gaps, the objective of this systematic review was to answer two clinically relevant questions: (1) Does BFR induce skeletal muscle hypertrophy in adults older than 50 years of age? (2) Does BFR improve muscle strength and/or physical function in adults older than 50 years?
Materials and Methods
Search Strategy and Criteria
We searched for potential research publications describing the clinical utility of BFR in the following databases: PubMed, Web of Science, Google Scholar, and Science Direct, using a Boolean equation with the search terms “blood flow restriction” OR “KAATSU” OR “ischemic training” AND “clinical” AND “elderly.” Once the title and abstract of each study were reviewed—and when they did not provide sufficient information regarding eligibility—the full-text article was reviewed. Two authors (BSB, MSS) independently conducted the search and cataloged all articles. Information collected from each article was sample size, age, and health status of the participants; exercise intervention used; and BFR application methods. Additionally, methods including the measurement of muscle mass, cross-sectional area, volume, circumference, and thickness were used to address our first research question regarding BFR’s effects on muscle hypertrophy. Changes in isometric and dynamic strength and torque and functional capacity, balance, gait speed, and dynamic movement task measurements were used to address our second research question regarding BFR’s effects on functionality and strength.
Articles were included if they were published in English between January 1, 1990 and January 1, 2019. Research designs included prospective randomized control trials, prospective cohort studies, or cross-sectional designs using BFR therapy with exercise interventions in adults 50 years and older. All articles included a control condition such as a pre-assessment, contralateral limb without BFR therapy, exercising control, or a sedentary control group to compare against BFR conditions. Studies were not excluded for different BFR methodologies such as occlusion pressures, duration, or frequency of application. Articles were excluded if they did not include a description of experimentation, were not full-text articles published in scientific peer-reviewed journals, were a case series, did not use BFR during rehabilitation/exercise, or did not include musculoskeletal outcome measures specific to our two research questions. The results of the search are reported in a Preferred Reporting Items for Systematic Reviews and Meta-analysis study flowchart [42] (Fig. 1). The search yielded 2189 articles and after duplicates were removed, 1574 articles were assessed for initial eligibility and 30 were retained (Table 1).
Fig. 1.
This PRISMA flowchart shows study selection.
Table 1.
Articles analyzing either skeletal muscle and/or functional performance are ordered by length of intervention and summarized below.
Methodological Quality Assessment
Two authors (BSB, MSS) used the Risk of Bias in Nonrandomized Studies of Interventions [60] and the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials [24] to jointly create an overall risk of bias score (low risk, moderate, or high risk). Two areas of special concern were patient selection and the presence and type of a reference standard or group. Studies that included more groups, enrolled a larger sample size, and had a longer duration were at less risk of bias (Table 2). Nearly two thirds of the studies were considered to be at moderate or high risk of bias because of research design, lack of randomization of participants, and the sparse use of multiple groups including non-BFR exercise controls and sedentary reference populations.
Table 2.
Risk of bias assessment for each included article
Study Outcomes
Our first aim was to understand if, and to what extent, does BFR induce muscle hypertrophy in adults older than 50 years. Muscle hypertrophy describes the increase in muscle size and is often measured as cross-sectional area, volume, thickness, circumferences, or mass. Twenty studies in this review quantified muscle size and were used to examine the first question. Study duration ranged from cross-sectional to 16 weeks, sample size ranged from 9 to 48 with a total of 413 participants (males n = 101; females n = 278; sex not reported n = 34) and average age was 63 years. In all, 80% of articles enrolled healthy participants, but patients in a coma [7], those with a spinal cord injury (incomplete tetraplegia) [22], and osteoarthritis (OA) [15, 56] were included.
Our second aim was to understand if muscle strength and physical function responded to BFR in adults older than 50 years. Muscle strength, or the ability to exert force, was measured as the maximal voluntary contraction force, maximal voluntary isometric contraction force, torque, muscle activation, or one repetition maximum; while functional performance included the 30 second sit-to-stand (30STS) and the 8 feet timed up and go (TUG). Twenty-five of 30 studies reported muscular strength outcome measures and eight studies included measures of the 30STS and/or TUG. Study duration ranged from cross-sectional to 16 weeks, sample size ranged from 6 to 56 with a total of 694 participants (males n = 205; females n = 455; sex not reported n = 34) and average age was 66 years. Overall, 74% of articles enrolled healthy participants, but patients with OA [9, 15, 55, 56], osteoporosis [52], cardiovascular disease [19], and sporadic inclusion body myositis [27] were included.
Percent changes and effect sizes were calculated for outcome variables when raw means and SDs for pre- and post-data were available. Percent changes were calculated using the equation: % change = [(post-mean – pre-mean)/ pre-mean] *100. Positive values indicate an increase while negative values indicate a decrease over time. Effect sizes were calculated using the equation: ES = (post mean – pre mean)/pre-SD. Effect sizes indicate the magnitude of difference between BFR and non-BFR group means, with larger numbers (that is, greater than 0.8) indicating a greater difference between values.
Results
Does BFR Induce Skeletal Muscle Hypertrophy in Adults Older than 50 Years?
Using muscle cross-sectional area, volume, mass, thickness, or limb circumference, 20 of 30 studies addressed the question of muscle hypertrophy and 15 of those studies reported increased skeletal muscle size after the BFR intervention with percent changes and effect sizes ranging from -5.5% to 17.5% and 0.11 to 3.6, respectively (Fig. 2) [4, 13-15, 22, 31, 34, 43, 46, 47, 69-73]. Additionally, studying 20 patients in a coma, Barbalho et al. [7] reported that passive mobilization using BFR better protected lower body muscles from atrophy. The contralateral limb, which did not receive BFR lost more than 25% of muscle thickness in an average of 11 days compared with the BFR treated limb which only lost 19% (effect size = 1.25). Three of 18 studies found no difference in muscle measurements compared with controls [56, 59, 67].
Fig. 2.
Twenty studies examining muscle size were separated by the magnitude of the effect of BFR on change in muscle size and the duration of the intervention. Data in blue represent studies with findings that report substantial positive effects of BFR on skeletal muscle size, while data in red represent no-difference (ND) or unsupportive findings of the first aim of our study; *p < 0.05; **p < 0.01, ***p < 0.001.
Does BFR Improve Muscle Strength and/or Physical Function in Adults Older Than 50 Years?
Of the 30 studies included, 25 addressed muscle strength and eight addressed physical function. Eighteen reported increases in muscle strength, with percent changes and effect sizes ranging from -5.2% to 42.0% and 0.55 to 4.34, respectively (Fig. 3) [4-6, 14, 15, 28, 33, 34, 46, 47, 49, 52, 56, 70-73, 75]. Six reported that BFR does not induce a greater increase in muscle strength than other non-BFR conditions [9, 13, 14, 55, 67, 69]. The only adverse effect was reported by Natsume et al. [43], who found a 5.2% reduction in maximal voluntary isometric contractions immediately after walking with BFR for 20 minutes. Performance of the TUG and 30STS improved with the addition of BFR [4, 5, 11, 15, 70, 75]. The effects of BFR were not different according to Bryk et al. [9], who reported a 1.2 second reduction in TUG time in patients with knee OA and Jørgensen et al. [27] reported no difference in TUG or 30STS performance in those with sporadic inclusion body myositis.
Fig. 3.
Twenty-five studies reported changes in muscle strength ●, four reported changes in chair-stand performance ■, and five reported changes in timed-up-and-go performance ▲. Each study is plotted according to the magnitude of change in response to BFR therapy and the duration of the intervention. Data in blue represent studies with findings that report substantial positive effects of BFR on skeletal muscle strength or performance, while data in red represent no-difference (ND) or unsupportive findings of the second aim of our study. For the chair-stand and timed-up-and-go tasks, negative values indicate a reduction in time to completion and an improvement in performance. *p < 0.05; **p <0 .01, ***p < 0.001; TUG = timed-up and-go; CS= chair-stand.
Discussion
BFR therapy is receiving increased attention and use as a therapeutic modality in sports medicine and has been the focus of more than 2000 publications since 2015. Available evidence for BFR use in athletes consistently shows that strength gains and muscle hypertrophy can be achieved in shorter periods of time with lower training volumes compared with traditional high-intensity resistance training [1, 40, 50, 64, 66]. Based on these cited benefits, BFR may be an effective intervention for older patients for whom high-intensity resistance exercise is contraindicated because of musculoskeletal disease or injury [70, 72, 73]. However, to date, the evidence supporting BFR’s use in older adults stems from studies with limited samples sizes and varied research designs putting these results at greater risk for bias. Therefore, this systematic review aimed to determine the documented effects of BFR on skeletal muscle size, strength, and function in older adults. Available evidence suggests BFR can induce positive adaptations to muscle size, strength, and physical performance in older adults.
Two important limitations of this body of evidence that clinicians and practitioners need to carefully consider are the heterogeneity of BFR protocols and the disparate participant ages and health conditions among the included studies. One example of BFR protocol heterogeneity is occlusion pressure, which can vary widely between days, exercise conditions, and participants. Some studies used a patient-dependent pressure ramp protocol while others relied on fixed pressure throughout the intervention, and these varying occlusion pressures make direct comparisons between study results difficult [35]. Much research on the ideal BFR methodology and application has already been published in young adults [8, 35, 37, 50], but to date no consensus exists for adults older than 50 years of age, which is a necessary next step to ensure practical and safe implementation in the clinical setting. Another important limitation to consider is the variability in participant age and health status. Despite the positive effects of BFR reported in most of the studies included in this review, the average age of participants was 64 years. The extent to which adults older than 80 years may respond to BFR is still unknown, which is of concern as this age group comprises a large proportion of orthopaedic patients. Furthermore, particular medical conditions may be more influential than others on BFR’s effects. For instance in patients with OA [9, 15, 55, 56] and those who were completely immobilized [7, 22], the percent change and effect sizes ranged from 3.3% to 42.0% and 0.45 to 1.9, respectively. In patients with sporadic inclusion body myositis [27] and osteoporosis [52], the percent change and effect sizes ranged from 9 to 24.25 and 0 to 0.68, respectively. Future studies are needed to specifically target adults older than 80 years who are healthy and battling a variety of diseases to better understand the potential utility of BFR as a clinical rehabilitation tool.
Most studies in this systematic review reported positive effects of BFR on muscle size in adults older than 50 years of age, with effect sizes ranging from moderate to large. A potential initial mechanism for these findings is mammalian target of rapamycin complex 1 (MTOR1) signaling, which increases muscle protein synthesis and has been shown to increase after BFR in younger [17] and older men [16]. However, other important mechanisms of muscle hypertrophy include anabolic and sex hormones, which have been shown to increase [40, 45, 51, 57] or not change [29, 51] after BFR in older adults. Older males have a blunted growth hormone response after BFR exercise compared with younger males [40], suggesting age could be an underlying factor influencing the incidence and magnitude of muscle hypertrophy in response to BFR. Furthermore, postmenopausal females have an added challenge to maintaining and building new muscle related to estrogen deficiency. In this systematic review, three studies exclusively enrolled postmenopausal females and found no change in muscle size between the BFR and comparative groups. Although this could indicate a limitation to BFR in this population, the comparative group for each of these studies engaged in a high-intensity exercise intervention, which influences interpretations of results. To fully understand the clinical utility of BFR for inducing muscle hypertrophy, the relationship between hormone status, sex, and age must be further characterized. Additionally, nearly 70% of papers included in this systematic review were at moderate or high risk of bias due to study design features. Future studies must employ larger sample sizes, participant randomization techniques, greater follow-up durations, and active recruitment of more diverse study participants to increase the generalizability of results while reducing the risk of bias.
The long-term goal of most exercise interventions in older adults is to improve muscular strength and functional performance. Most included studies demonstrated BFR’s ability to increase muscle strength, which has consistently been associated with reduced mortality rates in healthy and unhealthy adults [20, 41, 44]. Two included studies [9, 69] reported increases in muscle strength but those differences were not different than the comparative group, who engaged in high-intensity (> 70% one repetition of maximal voluntary contraction) resistance training. Furthermore, because lower body strength is closely linked to gait, balance, and coordination [18, 68], the observed BFR-related strength gains may also indirectly mitigate many of the factors associated with the risk of falling. The clinical advantages of BFR were apparent even in patients with OA as Bryk et al. [9] found BFR’s effects were not different from those elicited by high-intensity exercise for improving physical performance while substantially reducing patient-reported pain. Additionally, Yokokawa et al. [75] reported BFR training resulted in improvements in gait, reaction time, and balance in older adults that were not different when compared with a dynamic balance training program, while only patients in the BFR group benefited from substantial muscle strength gains.
Available evidence suggests BFR can induce muscle hypertrophy, thus increasing muscle strength and improving physical function in older adults. However, these findings must be considered carefully, as most studies were at moderate or high risk for bias and featured only small sample sizes. Future studies need to determine appropriate indications for prescription in older orthopaedic patients by extending the follow-up periods, enrolling larger and more diverse sample sizes, and using randomization techniques.
Acknowledgments
We thank Steve C. Friedman BA, and Lisa A. Royse PhD, for their editorial efforts on this manuscript.
Footnotes
Each author certifies that neither he or she, nor any member of his or her immediate family, has no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.
Each author certifies that his or her institution approved the reporting of this investigation and that all investigations were conducted in conformity with ethical principles of research.
This work was performed at the Missouri Orthopedic Institute, Columbia, MO, USA.
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