Dose-response relationship of blood flow restriction training on isometric muscle strength, maximum strength and lower limb extensor strength: A meta-analysis

Abstract

Objective: To perform a meta-analysis on the efficacy and dose-response relationship of blood flow restriction training on muscle strength reported worldwide.

Methods: Thirty-four eligible articles with a total sample size of 549 participants were included in the meta-analysis. This study was performed using the method recommended by the Cochrane Handbook (https://training.cochrane.org/handbook), and the effect size was estimated using the standardized mean difference (SMD) and using RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014).

Results: The meta-analysis showed that blood flow restriction training increased the lower limb extensor muscle strength [SMD = 0.72, 95%; confidence interval (CI): 0.43 to 1.00, p < 0.01], knee extensor isokinetic torque SMD = 0.48 [95% CI: 0.24 to 0.73, p < 0.01], knee flexor isokinetic torque SMD = 0.39 [95% CI: 0.11 to 0.67, p < 0.01], and squat one-repetition maximum [SMD = 0.28, 95% CI: 0.01 to 0.55, p < 0.01]. There was no publication bias. Evaluation of dose-response relationship showed that the training load, mode, frequency, duration, and maximum cuff pressure affected the muscle function.

Conclusion: blood flow restriction training. 16 significantly improved lower limb muscle strength, and the optimal training conditions consisted of a weight load smaller or equal to 30% of one-repetition maximum, training duration longer than 4 weeks, frequency of more than 3 times/week, and maximum cuff pressure lower than 200 mmHg.

Systematic Review Registration: website, identifier registration number.

1 Introduction

Blood flow restriction training was introduced in 1983 as a novel training method in which the blood flow is restricted by applying pressure to the proximal muscle extremities with a specially designed constricting device, such as blood pressure cuff or tourniquet (Sheng et al., 2019). The blood flow restriction increases the mass of exercising muscles (Manini and Clark, 2009). It is also known as KAATSU training, with the advantages of low training risk and intensity but high frequency (Manini and Clark, 2009; Abe et al., 2012). In recent years, bloo¹d flow restriction training has been widely used in competitive sports, public fitness, and rehabilitation. Studies have confirmed the beneficial effects of blood flow restriction training on athletes in track and field, soccer, rugby, tennis, handball, and basketball by improving the maximum strength and isokinetic torque strength of the upper and lower limb muscles (Kubota et al., 2008; Kubota et al., 2011; Xu and Wang, 2013; Pope et al., 2015; Tennent et al., 2017; Li et al., 2019; Wang et al., 2019). A meta-analysis by Wu et al. of 14 studies showed that blood flow restriction training increased the standard extensor strength of lower limbs and the cross-sectional area of quadriceps (Wu et al., 2019). Niu et al. conducted a meta-analysis of 47 studies and concluded that blood flow restriction training significantly increased muscles’ mass and maximum strength (Niu et al., 2020). Loenneke et al. found in a meta-analysis that 15%–30% one-repetition maximum (1RM)/maximal voluntary contraction (MVC) had a better muscle training effect (Abe et al., 2012). Similarly, Slysz et al. confirmed the effectiveness of blood flow restriction training on muscle hypertrophy and strength, with analysis of 47 studies (Slysz and Burr, 2016). Although the effects of blood flow restriction training on the body have been confirmed, there is still a lack of evidence-based on the “dose-response” relationship of blood flow restriction training (Manini and Clark, 2009). Duo to the above, this study is the first to systematically evaluate the intervention intensity, cycle, frequency, and pressure peak of blood flow restriction training, and conduct a four-item meta-analysis study on the effect of blood flow restriction training on lower limb muscle strength. In this study, a dose-effect relationship will be observed between blood flow restriction training and lower extremity muscle strength in order to evaluate the training effect more quantitatively (Aune et al., 2016) and to provide a more objective and reliable blood flow restriction training plan, in order to produce scientific and reliable results—quantitative guidance.

2 Methods

2.1 Search strategy and study selection

This meta-analysis was performed according to the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines (Cumpston et al., 2019). A computer-assisted literature search was performed in China National Knowledge Infrastructure, Wan-Fang Med Online, Baidu Scholar, Web of Science, PubMed, Elsevier, Embase, and EBSCOhost. The keywords were “pressurized training”, “blood flow restriction training”, “blood blockage; training”, and “KAATSU training”. The English keywords were “KAATSU training” [Title/Abstract] OR “blood flow restriction training” [Title/Abstract] OR “BFRT” [Title/Abstract] OR “blood flow restriction exercise” [Title/Abstract] OR “occlusion training” [Title/Abstract] “Restricted Leg Blood Flow” [Title/Abstract]. We searched articles published from inception to October 2022. All retrieved articles in Chinese and English were imported into EndNote (version X9, Clarivate Analytics) for deduplication. Two independent reviewers (HJX and ZZY) screened articles against the inclusion and exclusion criteria, and discrepancies were resolved by discussion and consensus with a third reviewer (SJ). The following data were extracted: 1) citation information of included studies, such as title, first author, journal, and time of publication; 2) baseline characteristics of participants, including a sample size of each group, and the age and sex of participants; 3) details of interventions such as duration, frequency, load, maximal cuff peak; 4) key elements of bias risk assessment; 5) outcome indicators and measures.

2.2 Inclusion criteria

According to the PICOS (Liu et al., 2017) principle (patient/population, intervention, comparison/control, outcome and study design), trials were eligible for inclusion if they met the criteria as follows: 1) participants were defined as healthy individuals; 2) the types of studies include randomized controlled trials (RCTs) or self-controlled trials, regardless of blinding or allocation concealment, and the control groups were daily activities or regular physical activities without interventions. 3) the outcomes measures of the trial included functional indicators include knee flexor (extensor) isokinetic torque, maximum squat strength, and lower limb extensor strength. 4) the selected articles were peer-reviewed publications written in English.

2.3 Exclusion criteria

Trials were excluded when they met any of the following exclusion criteria: 1) Trials without randomized, self-controlled, or randomized crossover design; 2) lack of appropriate outcome indicators; 3) conference abstracts and overviews; 4) articles with inappropriate subjects (animals).

2.4 Quality assessment

The quality of articles as indicated by the risk of bias in RCT was assessed using the method recommended by the Cochrane Handbook (https://training.cochrane.org/handbook). The articles were ranked at high, low, or unclear risk of bias. The low, high, and unclear risk of bias is represented by three colors in the evaluation plot, green for low, yellow for uncertain, and red for high.

2.5 Statistical analysis

RevMan, Computer program, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014) and using STATA software version 17 (STATA Corp, College Station, TX, USA) for data analysis. Q test was used to assess the heterogeneity of data in articles (α = 0.1). The effect size was calculated using different models based on the heterogeneity between studies. I² ≤ 50% (p ≥ 0.1) was regarded as minimal heterogeneity between studies, and a fixed-effects model was adopted. A random-effects model was used otherwise. The effect size was expressed as standardized mean difference (SMD), 95% CI, and subgroup analysis for moderators, with effect sizes of 0.2, 0.5, and 0.8 defined as small, medium, and medium-large, respectively.

3 Results

3.1 Literature review

A total of 1,070 English articles and 295 Chinese articles were retrieved, and 29 English articles (Abe et al., 2005; Beekley et al., 2005; Yasuda et al., 2005; Fujita et al., 2008; Madarame et al., 2008; Abe et al., 2010a; Abe et al., 2010b; Park et al., 2010; Sumide et al., 2010; Madarame et al., 2011; Tomohiro et al., 2011; Yasuda et al., 2011; Godawa et al., 2012; Keramidas et al., 2012; Martín-Hernández et al., 2012; Tetsuo et al., 2012; Luebbers et al., 2014; Yasuda et al., 2014; Barcelos et al., 2015; Fahs et al., 2015; Lixandrão et al., 2015; Vechin et al., 2015; Yasuda et al., 2015; Kim et al., 2016; Luebbers et al., 2017; Slysz and Burr, 2017; Bjørnsen et al., 2019; Harper et al., 2019; Schwiete et al., 2021; Teixeira et al., 2021) and 5Chinese articles (Liu et al., 2018; Lu et al., 2020; Zhang et al., 2020; Li et al., 2022; Tang and Qu, 2022) were included in the meta-analysis. The flow diagram of the study selection is shown in Figure 1.

FIGURE 1

3.2 Basic information of the included studies

A total of 34 articles with 49 studies (with some articles containing multiple studies) were included for 145 meta-analysis, with 549 participants in intervention groups and 549 participants in control groups. Participants were of mixed gender, age between 18 and 78 years and were males (70%) and were females (30%). RCT were used in all studies with blood flow restriction training as the intervention. The training load weight (based on one-repetition maximum) is divided into three categories: a low load (20%–50% 1RM), a medium load (50%–80% 1RM), and a high load (80%–100% 1RM). The training could be short-term training (1–2 weeks) or chronic, and the duration, frequency, and cuff pressure are shown in Table 1.

3.3 Bias risk assessment

The quality of 34 articles with RCT was evaluated with Cochrane risk assessment tool. Three articles mentioned allocation concealment, and the risk of bias was low. The remaining articles mentioned randomization through detailed methods, and allocation concealment was absent, therefore the risk of bias was unclear. In the 23 articles using blinding the risk of bias was low. All publications reported the loss of follow-up and were of high quality (Figure 2).

FIGURE 2

3.4 Overall effect of blood flow restriction training on lower limb muscle function

3.4.1 Muscular strength indicators

The functional indicators described in the 34 articles added to the present analysis were categorized into knee extensor isokinetic torque, knee flexor isokinetic torque, the lower limb extensor muscle strength, and squat one-repetition maximum (1RM). A total of 11 studies with 220 participants were included for the lower limb extensor muscle strength, with 11 individual effect sizes, an overall effect size of SMD = 0.72 [95% CI: 0.43 to 1.00, p < 0.01], and heterogeneity (I² = 51%, p = 0.02). Seventeen studies with 283 participants were included for knee extensor isokinetic torque, with 17 individual effect sizes, an overall effect size of SMD = 0.48 [95% CI: 0.24 to 0.73, p < 0.01], and no heterogeneity (I² = 24%, p = 0.18). A total of 13 studies with 208 participants were included for knee flexor isokinetic torque, with 13 individual effect sizes, an overall effect size of SMD = 0.39 [95% CI: 0.11 to 0.67, p < 0.01], and no heterogeneity (I² = 0%, p = 0.86). Fourteen studies with 249 participants were included for squat 1RM, with 14 individual effect sizes, an overall effect size of SMD = 0.36 [95% CI:0.10 to 0.62, p < 0.01], and no heterogeneity (I² = 0%, p = 0.93). This above are shown in Figure 3.

FIGURE 3

3.4.2 Dose-response relationship

Based on the included articles, the dose-response relationship was evaluated in the training load, training duration, training frequency, and maximum cuff pressure.

3.4.2.1 Effect of blood flow restriction training on knee extensor isokinetic torque

3.4.2.2 Effect of blood flow restriction training on knee flexor isokinetic torque

3.4.2.3 Effect of blood flow restriction training on lower limb extensor muscle strength

3.4.2.4 Effect of blood flow restriction training on squat 1-RM

3.5 Publication bias and sensitivity analysis

3.5.1 Publication bias

Begg’s funnel plot was used to assess the publication bias of knee extensor’s, knee flexor isokinetic torque, lower limb extensor muscle strength, and squat 1RM. The symmetrical funnel plots suggested no publication bias for the four indicators. This above are shown in Figure 4.

FIGURE 4

3.5.2 Sensitivity analysis

The sensitivity analysis is based on knee extensor’s, knee extensor’s, torque, lower limb extensor muscle strength, and squat 1RM. Sensitivity analysis was performed using the leave-one-out method, in which dubious literature was excluded one by one to test for the presence of literature that significantly influenced the conclusion. The results are shown in Figure 5, which shows that after excluding any study, the degree of bias of the point estimates of the new combined effect sizes obtained by subjecting the remaining studies to a new Meta-analysis was not significant, suggesting good robustness of the conclusion and that no single study significantly influenced the conclusion, so all included literature was retained. This above are shown in Figure 5.

FIGURE 5

4 Discussion

Blood flow restriction training had a positive effect on participant’s lower limb muscle function, and all studies showed moderate effect sizes for function improvement. Comparative analysis showed that Blood flow restriction training increased the knee extensor isokinetic torque, knee flexor isokinetic torque, lower limb extensor muscle strength, and squat 1RM. In particular, the improvement of lower limb extensor muscle strength was high and with low heterogeneity. Load measured by percentages of 1RM and MVC is an important factor influencing the training effect, and 20%–30% 1RM has been recommended for optimal training performance (Manini and Clark, 2009), which was confirmed in the present study. Abe et al. used 20% 1RM for a 2-week blood flow restriction training of healthy male participants (Abe et al., 2012). They found significant increases in the maximum squat strength (16.8%) and leg curl strength (22.6%) for 2 weeks (Zhang et al., 2020), similar to the training effect in another study using 30% 1RM over 10 weeks (Luebbers et al., 2017). Although the training effect increases with training load, an excessive load may not lead to beneficial results. Jessee et al. compared 50% 1RM with 30% 1RM and found little difference in muscle hypertrophy (Madarame et al., 2011; Jessee et al., 2018). Moreover, studies showed that blood flow restriction training did not increase muscle activation at high load (70% 1RM) (Takarada et al., 2002) and decreased muscle activation at > 70% 1RM (Dankel et al., 2017). In addition, blood flow restriction training at 80% 1RM showed no significant improvement in muscle hypertrophy and strength (Luebbers et al., 2014; Winchester et al., 2020). As muscle resistance increases, muscle contraction has internal restrictions on blood flow, and external cuff pressure may fail to produce a positive effect. In addition, excessive blood flow restriction causes severe fatigue (Teixeira et al., 2018). Based on previous findings (Niu et al., 2020), the effect may be optimal at training loads not exceeding 30% 1RM.

4.1 Training duration

The studies of the training duration showed that the effect size increased with the number of weeks of training and reached a maximum at ≥ 4 weeks. Blood flow restriction training increases not only muscle hypertrophy and strength but also the adaptation of muscles to physiological load. Therefore, the training should be performed in a low-load, high-frequency, and incremental manner.

4.2 Training frequency

The frequency of blood flow restriction training ranged from 2 to 5 times/week (5 days per week) (Yasuda et al., 2005; Liu et al., 2018). Fujita et al. found that the maximum strength of the knee extensor was increased after 6 days (twice a day) of training at 20% 1RM (Fujita et al., 2008). In contrast, blood flow restriction training to subjective exhaustion was reported to reduce training frequency (Winchester et al., 2020). Research has shown that although acute blood flow restriction training enhanced muscle activation, low-intensity blood flow restriction training was less effective than high-intensity resistance training in improving muscle strength; however, the effect of blood flow restriction training gradually appeared with the increase of training frequency (Fitschen et al., 2015). The present study showed that the performance was optimal at > 3 times/week.

4.3 Maximum cuff pressure

Cuff pressure is an important factor affecting blood flow restriction training and the blood flow restriction in extremities, and thus a fundamental condition of this training method. Cuff pressure causes difficulty in convective oxygen transport, leading to the accumulation of metabolites such as lactate and increased secretion of the growth hormone (Takano et al., 2005; Fatela et al., 2018), thus achieving similar effects as high-intensity exercises. The peak-value effect size varied in the range of cuff pressure (80–200 mmHg) applied in the analyzed studies, and the data suggest that a maximum cuff pressure ≤ of 200 mmHg had the best effect on increasing muscle function.

5 Practical limitations

Based on the above analyses, the following aspects should be noted in future studies. 1) A meta-analysis should be based on a comprehensive collection of previous studies, and the unavailability of unpublished articles and unreported negative results should always be addressed. 2) In this study, we only considered the effects of blood flow restriction training on muscle strength indicators, and future studies could include muscle function, safety, and gender differences. 3) The dose-response relationship for the elderly and rehabilitation populations needs to be further explored. 4) The participants in the included studies could have very different training status. 5) The age range was quite varied (18–78). Aging effects should be further concerned.

6 Conclusion

Blood flow restriction training significantly improved lower limb muscle strength. The optimal blood f1ow restriction training conditions observed in this meta-analysis were a training load of ≤30% 1RM, training duration of >4 weeks, training frequency of >3 times/week, and a maximum cuff pressure of ≤200 mmHg.

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