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Effects of Blood Flow Restriction Therapy for Muscular Strength, Hypertrophy, and Endurance in Healthy and Special Populations: A Systematic Review and Meta-Analysis

Perera, Edward BSc, MBBS*; Zhu, Xi Ming MBBS, MSc*; Horner, Nolan S. MD; Bedi, Asheesh MD; Ayeni, Olufemi R. MD, PhD, FRCSC; Khan, Moin MD, MSc, FRCSC

Author Information
Clinical Journal of Sport Medicine: September 2022 - Volume 32 - Issue 5 - p 531-545
doi: 10.1097/JSM.0000000000000991
  • Free

Abstract

INTRODUCTION

Traditionally, the gold standard for inducing muscle hypertrophy and improving strength has been through high-intensity resistance training (HIRT). This generally involves loads between 70% and 85% of 1 repetition maximum (1RM) performing 6 to 8 repetitions.1 However, in recent years, blood flow restriction (BFR) training offers an alternative to conventional resistance training. Blood flow restriction (or Kaatsu) training involves wrapping the proximal aspect of the limb with a tourniquet or pressure cuff to partially or completely occlude blood flow to the limb.2 Performing low-intensity resistance training (LIRT), involving loads of 20% to 30% of 1RM, in the presence of limb ischemia has demonstrated increased muscle hypertrophy and strength, comparable with that of HIRT.3 Fry et al4 suggested that muscle protein synthesis was stimulated by BFR training because of enhanced mTORC1 signaling. It is suggested that acute swelling of muscle cells triggers this signaling pathway, leading to hypertrophic effects similar to those seen in HIRT.5–7

Blood flow restriction training is of potential use in older patients and those undergoing physical rehabilitation, where the heavy loads of HIRT are not required.8 Several studies have demonstrated that BFR training results in increased muscle strength in elderly populations.9–11

Nakajima et al reported the most commonly reported side effect of BFR was subcutaneous hemorrhages (13.1%). However, more serious complications such as venous thrombus, pulmonary embolus, rhabdomyolysis, and deterioration of ischemic heart disease have been reported in rare cases (<0.06%) of individuals undertaking BFR.12

Findings from previous reviews suggest that although low-intensity BFR (LI-BFR) training can produce strength improvements, it remains inferior when compared with HIRT.13 Others looked at its use in the elderly or those with musculoskeletal conditions where high loads are not suitable. Low-intensity BFR training has shown a significant effect to increase muscle hypertrophy and strength.9,14

However, previous systematic reviews on the subject are methodologically flawed, including limited number of studies, using restrictive inclusion criteria, failing to publish a prospective protocol, and/or using outdated search strategies.9,13,14 The objective of this review was to compare the effectiveness of various BFR training protocols relative to other forms of strength training on muscle strength, hypertrophy, and endurance. We hypothesize that LI-BFR training will be superior for muscle hypertrophy and strength when compared with similar nonoccluded training protocols. However, overall, we expect HIRT to remain the most effective training to induce muscular strength and hypertrophy. We hypothesize that BFR training will result in greater improvements in endurance than endurance training alone.

METHODS

This systematic review and meta-analysis has been registered with PROSPERO (ID: CRD42018115849). We followed the reporting guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.15

Search Strategy

We conducted a search of MEDLINE, Embase, and PubMed from the earliest records until October 28, 2018. A repeat search of PubMed was performed on April 16, 2019, to capture any recently published studies. Search terms and subject headings used were BFR, vessel occlusion, Kaatsu, exercise, resistance training, muscle strength, and hypertrophy (Table 1).

TABLE 1. - Search Strategy
MEDLINE Embase PubMed
1. Regional blood flow
2. Muscle blood flow.mp.
3. Blood flow restriction.mp.
4. Therapeutic occlusion
5. Blood vessel occlusion.mp.
6. Hypoxia
7. Intermittent hypoxia.mp.
8. Kaatsu.mp.
9. Exp *EXERCISE
10. Exp *exercise therapy
11. Exp physical fitness
12. Training.mp.
13. Exp *resistance training
14. Exp *muscle strength
15. Exp muscle strengthening exercises
16. Exp sports
17. Muscle hypertrophy.mp.
18. Muscle hyperplasia.mp
19. Hyperplasia
20. Hypertrophy
21. Strength.mp.
22. 1 or 2 or 4 or 5 or 6 or 7
23. 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16
24. 17 or 18 or 19 or 20 or 21
25. 22 and 23
26. 24 and 25
27. 26 or 3 or 8
28. Limit 27 to English language
Results 755
Date October 28, 2018
1. Blood flow
2. Muscle blood flow
3. Blood flow restriction.mp.
4. Blood vessel occlusion
5. Blood vessel occlusion/th (therapy)
6. Intermittent hypoxia
7. Kaatsu.mp.
8. Exp *exercise
9. Exp dynamic exercise
10. Exp fitness
11. Exp *training
12. Exp *resistance training
13. Exp weight lifting
14. Exp *muscle strength
15. Exp athleteor exp basketball playeror exp body builderor exp boxeror exp cyclistor exp football playeror exp hockey playeror exp judokaor exp marathon runneror exp runneror exp skieror exp soccer playeror exp wrestler
16. Exp rowing
17. Exp *muscle hypertrophy
18. Muscle hyperplasia.mp.
19. Hyperplasia
20. Hypertrophy
21. Exp strength
22. 1 or 2 or 4 or 5 or 6
23. 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16
24. 17 or 18 or 19 or 20 or 21
25. 22 and 23
26. 24 and 25
27. 26 or 3 or 7
28. Limit 27 to (human and English language)
Results 503
October 28, 2018
1. Blood flow
2. Muscle blood flow
3. Blood vessel occlusion
4. Hypoxia
5. Exercise
6. Training
7. Resistance training
8. Weight lifting
9. Muscle strength
10. Athlete
11. Muscle hypertrophy
12. Muscle hyperplasia
13. Hypertrophy
14. Hyperplasia
15. BFR
16. Kaatsu
17. 1 or 2 or 3 or 4
18. 5 or 6 or 7 or 8 or 9 or 10
19. 11 or 12 or 13 or 14
20. 17 and 18
21. 19 and 20
22. 21 or 15 or 16
23. Limit 22 to humans and English language
Results 480
October 27, 2018

We defined BFR training to include any form of training where limb vessel blood flow was occluded through some form of mechanical device (eg, tourniquet or pneumatic pressure cuff). Any level of vessel occlusion was included, either partial (occluding venous flow partially or completely) or complete (complete occlusion of arterial and venous flow).

Inclusion and Exclusion Criteria

Inclusion and exclusion criteria were established a priori. The inclusion criteria were (1) randomized controlled trials (RCTs); (2) any publication to date; (3) studies where at minimum one of the arms of the RCT were treated with BFR therapy; (4) studies reporting on at minimum one of the following outcomes: muscle strength/power, muscular hypertrophy, endurance, or a physical function measure; (5) any patient population; and (6) articles published in peer-reviewed English language scientific journals.

The exclusion criteria were (1) nonhuman/cadaveric studies, (2) non-English language studies, (3) BFR treatment not relating to the musculoskeletal system or musculoskeletal outcomes (muscle hypertrophy, changes in strength, etc), and (4) any compounding mechanisms such as the use of known performance enhancing supplements or combination of BFR with altered partial pressures of oxygen.

Data Collection and Extraction

Two authors (EP and MZ) independently screened articles by title, abstract, and full text. In the event of a disagreement, a consensus was reached with a third author's (MK) analysis. The 2 authors independently extracted data which included study characteristics, participant demographics, sample size, intervention, frequency, intensity, time and type of exercise, duration and follow-up of intervention, pressure or percentage of arterial occlusion of device used, outcomes reported, and physiological results.

Assessment of Methodological Quality

Risk of bias was assessed by 2 authors (EP and MZ) at the outcome level using the Cochrane risk of bias tool for randomized trials.16 A rating of low, high, or unclear risk was given based on performance bias, detection bias, attrition bias, reporting bias, and other bias based on in-text evidence.

Statistical Analyses

Data were collated in a Windows Excel document (version 16.20, Microsoft, 2018) and then statistical analyses were performed using RevMan (Review Manager Version 5.3, The Cochrane Collaboration, 2014) for calculation of the difference in preintervention and postintervention mean and SD values. Where correlation coefficients were required for calculation of changes from baseline, a comparable correlation coefficient was extracted from another study within the analysis.17 Both fixed-effects and random-effects models for summary estimates were used dependent on heterogeneity, with mean difference (MD) used for continuous outcomes. Summary measures with corresponding 95% confidence intervals (CIs) and P values are presented in forest plots. A P < 0.05 was considered statistically significant.

Strength of Agreement

A Cohen kappa (κ) coefficient was used to calculate interobserver agreement at all stages according to Landis et al.18

Heterogeneity

The Ι2 statistic was used to measure the heterogeneity of studies included in meta-analyses. The Ι2 test was categorized as no, low, moderate, or high heterogeneity based on the criteria from Higgins et al.19

RESULTS

Eligibility

After a comprehensive search of databases, a total of 1748 studies were identified. After the removal of duplicates, 1084 studies were suitable for screening (Figure 1). From this selection, 53 studies were included in the final systematic review, of which 33 studies were used in the quantitative meta-analyses. Of the remaining 20 studies, there was insufficient overlap in reported outcomes to perform quantitative11,20–40 analysis.41–71

F1
Figure 1.:
Flow diagram of study selection and exclusion.

Interobserver agreement was considered to be moderate at all 3 stages: at the title stage with κ = 0.599 (SE = 0.028; CI, 0.543-0.655), at the abstract stage with κ = 0.6 (SE = 0.052; CI, 0.498-0.701), and at the full-text stage with κ = 0.52 (SE = 0.093; CI, 0.342-0.706).18

Study Characteristics

The total number of participants included in this review was 1337. Of these, the mean age and SD of participants was 36.0 ± 19.4 years, with 64.4% being men. The mean length of intervention was 6.8 ± 2.8 weeks, with the length of follow-up being 7.4 ± 3.8 weeks (Table 2). The mean frequency of training sessions was 3.7 ± 2.8 sessions per week, with a range from 2 to 12 sessions per week. Thirty-seven studies reported occlusion in mm Hg, with a mean pressure of 157.88 mm Hg and a range of 56 to 300 mm Hg. Eleven studies reported the percentage of arterial occlusion pressure (AOP) with a mean of 57.27% of AOP. Three studies used the percentage of maximal tightness with a mean of 71.67% of maximal tightness of strapping. One final study reported overlap of strapping, measuring 76 mm of overlap. Most studies favored intervention focusing on strength training with 28 of the protocols incorporating lower-body strength training and 16 incorporating upper-body strength training (Table 3).

TABLE 2. - Study Characteristics of All Studies Included in the Review
Author, Year Journal Location Sample Size Mean Age (±SD) Duration of Intervention in wk (Length of Follow-up in wk)
Abe, 2010 J Geriatr Phys Ther Japan 19 6 (6)
Abe, 2006 J Appl Physiol Japan 18 21.3 (2.8) 3 (3)
Abe, 2010a J Sports Sci Med Japan 19 23 (1.7) 8 (8)
Araujo, 2015 Age Brazil 28 54 (4) 8 (8)
Barbosa, 2018 J Vasc Access Brazil 26 60.7 (9.46) 8 (8)
Barcelos, 2015 Eur J Appl Physiol Brazil 48 8 (8)
Behringer, 2017 J Strength Cond Res Germany 25 23.7 (2.2) 6 (6)
Bryk, 2016 Knee Surg Sports Traumatol Arthrosc Brazil 34 61.4 (6.85) 6 (6)
Clark, 2011 Scand J Med Sci Spor United States 16 23.9 (1.59) 4 (4)
Clarkson, 2017 J Sci Med Sport Australia 19 69.5 (6.5) 6 (6)
Colomer-Proveda, 2017 Eur J Appl Physiol Spain 22 23.4 (2.81) 4 (4)
Counts, 2016 Muscle Nerve United States 7 23 (3) 8 (8)
de Oliveira, 2016 Scand J Med Sci Spor Brazil 37 23.8 (4) 4 (6)
Fahs, 2015 Clin Physiol Funct Imaging United States 18 55.3 (7.14) 6 (6)
Farup, 2014 Scand J Med Sci Spor Denmark 10 25.5 (3) 6 (6)
Fitschen, 2014 Clin Physiol Funct Imaging United States 30 31.6 (9) 5 (6)
Fujita, 2008 Int J KAATSU Training Res Japan 16 21.7 (3.05) 1 (1)
Giles, 2017 Br J Sports Med Australia 79 27.6 (5.35) 8 (26)
Hill, 2018 Eur J Appl Physiol United States 36 22.4 (1.6) 4 (5)
Hunt, 2013 J Appl Physiol England 9 22 (3) 6 (6)
Kang, 2015 J Phys Ther Sci Republic of Korea 17 25.2 (3.84) 6 (6)
Kim, 2016 J Strength Cond Res United States 31 22.4 (3) 6 (11)
Ladlow, 2018 Front Physiol England 28 30.5 (6.51) 3 (3)
Laswati, 2018 Chinese J Physiol Indonesia 18 32.4 (2.85) 5 (5)
Laurentino, 2008 Int J Sports Med Brazil 16 23 (3.39) 8 (8)
Lixandrao, 2015 Eur J Appl Physiol Brazil 52 27.9 (8.51) 12 (12)
Luebbers, 2017 J Strength Cond Res United States 25 15.9 (1.2) 6 (6)
Luebbers, 2014 J Strength Cond Res United States 62 20.3 (1.1) 7 (7)
Madarame, 2011 Acta Physiol Hung Japan 15 20.3 (1.82) 10 (11)
Madarame, 2008 Med Sci Sports Exerc Japan 15 21.7 (3.36) 10 (10)
Manimmanakorn, 2013 Eur J Appl Physiol Thailand 36 20.2 (3.3) 5 (7)
Martin-Hernandez, 2013 Scand J Med Sci Spor Spain 39 20.6 (1.73) 5 (5)
Moore, 2004 Eur J Appl Physiol Canada 8 19.5 (0.4) 8 (8)
Ozaki, 2011 Angiology Japan 23 66.9 (1) 10 (11)
Ozaki, 2011a J Gerontol A Biol Sci Med Sci Japan 18 65.8 (1) 10 (10)
Ozaki, 2013 Eur J Appl Physiol Japan 14 23.5 (0.707) 6 (6)
Paton, 2017 Eur J Appl Physiol New Zealand 16 25 (7) 4 (4)
Sakamaki, 2011 J Sports Sci Med Japan 17 21.2 (1.9) 3 (3)
Scott, 2017 J Strength Cond Res Australia 18 19.8 (1.5) 5 (5)
Segal, 2015 Geriatr Orthop Surg Rehabil United States 41 56.1 (7.7) 4 (4)
Segal, 2015a PM R United States 40 55.3 (6.45) 4 (4)
Sumide, 2009 J Sci Med Sport Japan 21 22.1 (1.8) 8 (8)
Thiebaud, 2013 Clin Physiol Funct Imaging United States 14 60.7 (2) 8 (8)
Vechin, 2015 J Strength Cond Res Brazil 23 64.3 (3.48) 12 (12)
Weatherholt, 2013 Med Sci Sports Exerc United States 40 21.65 (2.3) 8 (8)
Yasuda, 2010 Clin Physiol Funct Imaging Japan 10 25.7 (4.93) 2 (2)
Yasuda, 2016 Oncotarget Japan 30 70 (6.35) 12 (12)
Yasuda, 2012 PLoS One Japan 10 22 (2) 6 (7)
Yasuda, 2014 Scand J Med Sci Spor Japan 19 69.4 (6.82) 12 (12)
Yasuda, 2015 J Gerontol A Biol Sci Med Sci Japan 17 70 (5.71) 12 (12)
Yasuda, 2011 Clin Physiol Funct Imaging Japan 30 24.1 (2.05) 6 (6)
Yasuda, 2015a Springerplus Japan 14 69.5 (6.52) 12 (12)
Yokokawa, 2008 Biosci Trends Japan 44 70.6 (4.71) 8 (8)
Lowercase letters indicate different studies with the same author and year of publication.

TABLE 3. - Study Protocol Details, Listing Frequency, Intensity, Time, and Type of Exercise Performed
Author, Year % Males Intervention Protocol Duration of Intervention in wk (Frequency Per wk) Protocol Intensity
Abe, 2010 21.1 Walking 6 (5) Treadmill for 20 min
No additional routine
67 m/min
Abe, 2006 100 Walking 3 (12) Treadmill, 5 × 2 min bouts
Same protocol without BFR
50 m/min
Abe, 2010a 100 Cycling 8 (3) 15 min
Same protocol without BFR
40% V̇o 2 Max for
Araujo, 2015 0 Water-based exercise 8 (3) BFR: 4x (30-15-15-15)
Same protocol without BFR
No additional routine
Perceived effort
9-11 on the standard Borg scale (6-20)
Barbosa, 2018 46.2 BFR elbow flexion, tennis ball squeeze, and handgrip exercises 8 (5) 6 × 10 tennis ball squeezes (5 squeezes added each wk); elbow flexion 3 × 10; and handgrip exercises
Same protocol without BFR
Handgrip exercises 40% 1RM 3 × 20 in 1 min
Barcelos, 2015 100 BFR knee extensions 8 One set to concentric failure
One set to concentric failure
3 sets to concentric failure
3 sets to concentric failure
No additional routine
20% 1 RM
50% 1 RM
20% 1 RM
50% 1 RM
Behringer, 2017 100 BFR sprints 6 (2) 6 × 100 m
Same protocol without BFR
60%-70% max sprint speed
Bryk, 2016 0 BFR calf raise, knee extensions, hip abduction, and core training 6 (3) 3x variable reps
Same protocol without BFR
30% 1RM
70% 1RM
Clark, 2011 87.5 BFR knee extension
Same protocol without BFR
4 (3) 3x volitional failure (30-50 reps)
3x volitional failure (8-12 reps)
30% 1RM
80% 1RM
Clarkson, 2017 57.9 BFR walking 6 (4) 10 min walking
Same protocol without BFR
4 km/h
Colomer-Proveda, 2017 100 BFR calf raise 4 (3) 4x (30-15-15-15)
Same protocol without BFR
No additional routine
25% MVC
Counts, 2016 57.1 BFR elbow flexion 8 (2) 4x (30-15-15-15)
Same protocol with different pressure BFR
30% 1 RM
de Oliveira, 2016 59.5 BFR cycling 4 (3) 2 × 5 reps, and 1 rep added each wk
2 × 5 reps, and 1 rep added each wk
30% Pmax
1 set 30% Pmax
1 set 95%-110% Pmax
Fahs, 2015 66.7 BFR knee extension 6 2 wk 2 sets, 2 wk 3 sets, and 2 wk 4 sets
Same protocol without BFR
30% 1RM
Farup, 2014 80 BFR elbow flexion 6 (3) 4x volitional failure
Same protocol without BFR
40% 1RM
Fitschen, 2014 16.7 BFR calf raise, leg press, knee extension, and knee flexion 5 (3) 1st session: 30 repetitions
2nd session: 2x (30-15)
3rd session: 3x (30-15-15)
2 wk: 4x (30-15-15-15)
2 wk: 4x (30-20-20-20)
Same protocol with intermittent BFR
30% 1RM
Fujita, 2008 100 BFR knee extension
Same protocol without BFR
1 (12) 4x (30-15-15-15) 20% 1RM
Giles, 2017 45.6 BFR leg press and knee extension 8 (3) 4x (30-15-15-15)
3x 7-10
30% 1RM
70% 1RM
Hill, 2018 0 BFR elbow flexion 4 (3) 4x (30-15-15-15)
Same protocol without BFR
No additional routine
30% eccentric torque peak
30% concentric torque peak
Hunt, 2013 100 BFR calf raise 6 (3) 3x volitional failure
No additional exercise
30% 1RM
Kang, 2015 29.4 BFR lunges and squats 6 (3) 30 min of sets of 10-15 reps
Same protocol without BFR
RPE 11-13
Kim, 2016 100 BFR cycling
Same protocol without BFR
No additional routine
6 20 min
20 min
30% HRR (heart rate reserve)
3 wk: 60% HRR
3 wk: 70% HRR
Ladlow, 2018 100 BFR leg press and knee extension
Deadlift, back squat, and lunges
3 (9) 4x (30-15-15-15)
4x 6-8
30% 1 RM
Target 6-8 reps
Laswati, 2018 100 BFR elbow flexion 5 (2) 4x (30-15-15-15)
Same protocol without BFR
3 × 12
30% 1RM
70% 1RM
Laurentino, 2008 100 BFR knee extension 8 (2) 3 wk: 3 × 12
2 wk: 4 × 12
1 wk: 5 × 12
2 wk: 3 × 12
3 wk: 3 × 6
2 wk: 4 × 6
1 wk: 5 × 6
2 wk: 3 × 6
60% 1RM
80% 1RM
Lixandrao, 2015 100 BFR knee extension
Same protocol without BFR
12 (2) 2-3x 15 20% 1RM
40% 1RM
Luebbers, 2017 88 BFR squats
Same protocol without BFR
6 (2) Monday 3 × 10
Friday 3 × 3
4x (30-15-15-15)
65%, 70%, and 75% 1RM
80%, 85%, and 90% 1RM
2 wk: 20% 1RM
2 wk: 25% 1 RM
2 wk: 30% 1RM
Luebbers, 2014 100 BFR leg press, knee extension, knee flexion, bench press, elbow extension, and elbow flexion
Same protocol without BFR
7 (4) Customized protocol: Low repetitions Customized protocol: High % 1RM
Madarame, 2011 100 BFR leg press
Same protocol without BFR
2 2 wk: 3x (30-15-15)
6 wk: 4x (30-15-15-15)
1 wk: 4x (30-15-15-15)
1 wk: 4x (30-15-15-15)
30% 1RM
30% 1RM
30% 1RM + 5.5 kg
30% 1RM + 11 kg
Madarame, 2008 100 BFR knee extension, knee flexion, and elbow flexion
Same protocol without BFR
10 (2) 3 × 10 50% 1RM
Manimmanakorn, 2013 0 BFR knee extension and knee flexion
Same protocol without BFR
5 3x volitional failure 20% 1RM
Martin-Hernandez, 2013 100 BFR knee extension
Same protocol without BFR
No additional routine
5 (2) 4x (30-15-15-15)
3 × 8
20% 1RM
80% 1 RM
Moore, 2004 100 BFR elbow flexion
Same protocol without BFR
8 (3) 1 wk: 2 × 10, 1x volitional failure
1 wk: 3 × 10, 1x volitional failure
1 wk: 4 × 10, 1 × volitional failure
5 wk: 4 × 10, 2x volitional failure
50% 1RM
Ozaki, 2011 21.7 BFR walking
Same protocol without BFR
10 (4) 20 min 45% HRR
Ozaki, 2011a 0 BFR walking
Same protocol without BFR
10 (4) 20 min 4.5 km/h at 1.6° incline
Ozaki, 2012 100 BFR Bench press 6 (3) 4x (30-15-15-15)
3 × 10
30% 1RM
75% 1RM
Paton, 2017 62.5 BFR running
Same protocol without BFR
4 (2) 2 × 5 (30 s run, 30 s rest) 80% PRV (peak run velocity)
Sakamaki, 2011 100 BFR walking
Same protocol without BFR
3 (12) 5 × 2 min 50 m/min
Scott, 2017 100 BFR Squats
Same protocol without BFR
5 (3) 4x (30-15-15-15) 5 sessions: 20
5 sessions: 25% 1RM
5 sessions: 30% 1RM
Segal, 2015 100 BFR leg press
Same protocol without BFR
4 (3) 4x (30-15-15-15) 30% 1RM
Segal, 2015a 0 BFR leg press
Same protocol without BFR
4 (3) 4x (30-15-15-15) 30% 1 RM
Sumide, 2009 100 BFR SLR training, hip joint ABD, and hip joint ADD
Same protocol without BFR
8 (3) 20 × (20 repetitions SLR and ABD; 5 s max squeeze ADD) 20% 1RM
Thiebaud, 2013 0 BFR knee extension, knee flexion, bench press, hip flexion, hip extension, seated row, and seated shoulder press
Same protocol without BFR
8 (3) Upper body: 3x (30-15-15)
Lower body: 3 × 10
Elastic band ∼10%-30% 1RM
Vechin, 2015 56 BFR leg press
Same protocol without BFR
No additional routine
12 (2) 4x (30-15-15-15) 6 wk: 20% 1RM
6 wk: 30% 1RM
Weatherholt, 2013 42.5 BFR elbow flexion, elbow extension
Same protocol without BFR
No additional routine
8 (3) 3 × 15 20% 1 RM
Yasuda, 2010 100 BFR bench press
Same protocol without BFR
2 (12) 4x (30-15-15-15) 30% 1RM
Yasuda, 2016 0 BFR knee extension, squats
Same protocol without BFR
No additional routine
12 (2) 4x (30-15-15-15) 5-9 on the Omnibus resistance for active muscle scale
Yasuda, 2012 100 BFR elbow flexion
Same protocol without BFR
6 (3) 4x (30-15-15-15) 30% 1RM
Yasuda, 2014 26.3 BFR leg press and knee extension
No additional routine
12 (2) 4x (30-15-15-15) 20%-30% 1RM
Yasuda, 2015 17.6 BFR elbow flexion, elbow extension
Same protocol without BFR
12 (2) 4x (30-15-15-15) “Heavy (green)” band for men and “thin (yellow)” band for women
Yasuda, 2011 BFR bench press
Same protocol without BFR
No additional routine
6 (3) 4x (30-15-15-15) 30% 1RM
Yasuda, 2015a 0 BFR elbow extension, elbow flexion
Same protocol without BFR
12 (2) 4x (30-15-15-15) “Thin (yellow)” band
Yokokawa, 2008 BFR knee flexion, knee extension, calf raise, half squat, lunges, and alternating knee lifts to chest, crunches
Calf raise, dynamic balance exercise and functional ankle strengthening
8 (2) Customized program: 15 min on, 5 min rest, and 15 min on Customized program
Lowercase letters indicate different studies with the same author and year of publication.
ABD, abduction training; ADD, adduction training; SLR, straight leg raise.

Quality and Risk of Bias

Of the 53 studies, 94.3% demonstrated low risk regarding reporting bias; 52 of 53 studies were categorized as low risk of bias for the completeness of outcome data.

Thirty-seven of the 53 studies had insufficient data on randomization and were categorized as unclear risk of bias. Lack of detail in reporting suggested an unclear level of selection bias in 69.8% of studies.

In the assessment of performance and detection bias, 90.6% of studies demonstrated high risk of bias due to lack of blinding. The absence of a tourniquet in the control arms made blinding to intervention null for both participant and assessor, leading to high risk of bias (Table 4).

TABLE 4. - Risk of Bias
Lowercase letters indicate different studies with the same author and year of publication. ‟+” indicates low risk of bias. ‟-” indicates high risk of bias. ‟?” indicates unclear risk of bias.

Muscular Strength

A meta-analysis of 8 studies included 16 comparisons and a total of 358 participants, evaluating the change in muscular strength regarding 1RM between LI-BFR versus HIRT (Figure 2). Our analysis demonstrated a statistically significant improvement in HIRT when pooling upper-body and lower-body training (MD = 5.34 kg; 95% CI, 2.58-8.09; P < 0.01; Ι2 = 93%).

F2
Figure 2.:
Change in 1RM (kg) for LI-BFR training versus HIRT. *Capitalized letters indicate the same study but different protocols.

Subgroup analysis for lower-body training demonstrated a significant improvement favoring HIRT (MD = 6.32 kg; 95% CI, 1.48-11.17; P = 0.01; Ι2 = 94%). The upper-body subgroup supported this, also demonstrating a significant difference in favor of HIRT (MD = 4.28 kg; 95% CI, 3.6-4.96; P < 0.01; Ι2 = 0%). Bryk et al included a clinical sample of participants who had osteoarthritis and demonstrated a statistically significant difference in favor of BFR training.27

One hundred ninety-one participants across 6 studies made 12 comparisons between change in torque in LI-BFR training and LIRT (Figure 3). The overall MD was 9.94 N·m (95% CI, 5.43-14.45; P < 0.01) in favor of LI-BFR, when combining upper and lower limb subgroups, with moderate heterogeneity (Ι2 = 58%). A significant improvement in torque of the LI-BFR group compared with that of the LIRT group was seen in knee extension with a MD of 11.26 N·m (95% CI, 5.6-16.92; P < 0.01). In elbow flexion, there was a trend favoring the LI-BFR group, demonstrating a MD of 5.85 N·m (95% CI, −4.26 to 15.96; P = 0.26); however, this did not achieve statistical significance. Although heterogeneity of the subgroups was low for knee extension (Ι2 = 48%) and high elbow extension (Ι2 = 84%), there was no heterogeneity between the subgroups (Ι2 = 0%).

F3
Figure 3.:
Change in torque (N·m) for LI-BFR training versus LIRT. *Capitalized letters indicate the same study but different protocols.

Change in torque was also compared between LI-BFR training and HIRT in 3 studies, with 10 comparisons and 259 participants (Figure 4). The overall MD was 6.35 N·m (95% CI, 0.5-12.3; P = 0.04) favoring HIRT. Giles et al37 featured clinical participants with patellofemoral syndrome pain and demonstrated a statistically significant increase in torque favoring BFR training.

F4
Figure 4.:
Change in torque (N·m) for LI-BFR training versus HIRT. *Capitalized letters indicate the same study but different protocols.

Muscular Hypertrophy

A total of 314 participants from 11 studies with 15 comparisons investigated the changes in muscle cross-sectional area (CSA) between BFR training versus nonocclusive training (Figure 5). Ten studies used magnetic resonance imaging and 1 used peripheral quantitative computed tomography for calculation of CSA. The pooled MD in CSA was 0.96 cm2 (95% CI, 0.21-1.7; P = 0.01; I2 = 42%) favoring the BFR training groups.

F5
Figure 5.:
Change in CSA (cm2) for BFR training versus nonoccluded training. *Capitalized letters indicate the same study but different protocols. aLowercase letters indicate different studies with the same author and year of publication.

A significant increase in CSA was seen in the LI-BFR training group compared with the LIRT group (4 studies with 95 participants) with MD of 1.06 cm2 (95% CI, 0.14-1.99; P = 0.02; Ι2 = 13%). The BFR walk training group (3 studies with 76 participants) also saw a significantly greater MD of 2.80 cm2 (95% CI, 1.21-4.39; P = 0.0006; Ι2 = 0%) compared with the nonoccluded group. However, the increase in muscle CSA was significantly greatest in the HIRT group compared with LI-BFR training (4 studies with 143 participants) with a MD of 2.9 cm2 (95% CI, 0.77-5.02; P < 0.01; Ι2 = 0%). Heterogeneity for difference between subgroups was high (Ι2 = 88.8%). The sample from the study by Ladlow et al42 included participants with lower limb injuries and demonstrated a statistically significant increase favoring HIRT as opposed to LI-BFR training. Yasuda et al (2015) and Ozaki et al (2011) and (2011a) all had old age populations, and all individually showed statistically significant MD favoring BFR training.11,53,66

Endurance

Three studies including 111 participants compared BFR endurance training versus endurance training alone (Figure 6) using V̇o2 maximum. The results favored the BFR group with a MD of 0.37 mL/kg/min (95% CI, −0.97 to 3.17; P = 0.64); however, this did not reach statistical significance.

F6
Figure 6.:
Change in V̇o 2 max (mL/kg/min) for blood flow restricted endurance training versus endurance training. *Capitalized letters indicate the same study but different protocols. Lowercase letters indicate separate studies.

DISCUSSION

This study demonstrated significantly greater improvement in muscular strength and hypertrophy with HIRT when compared with LI-BFR training. However, when compared with a similar low-intensity routine, BFR training is significantly superior to nonoccluded programs. The case for augmentation of endurance training with vascular occlusion was not statistically different.

Our findings for muscular strength produced mixed results when comparing BFR with nonoccluded resistance training. In both pooled and individual results for 1RM, for upper-body and lower-body exercises, HIRT was found to be significantly more effective than LI-BFR training, with the greatest effect seen in lower-body exercises. However, it should be noted that all analyses for muscular strength demonstrated high heterogeneity. The potential sources of heterogeneity include the large range of ages (15.9-64.3 years), frequency of training per week (2-12 times), and duration of intervention (1-12 weeks).

Regarding muscle torque, although LI-BFR resistance training demonstrated a significantly greater MD when compared with LIRT, LI-BFR remained significantly inferior to HIRT. These results are in keeping with the works of Kubo et al who evaluated the effects of strength training in LI-BFR versus HIRT and Centner et al who analyzed LI-BFR versus LIRT.9,72

Our pooled findings suggest that BFR training is significantly superior to nonoccluded training regarding muscular hypertrophy. This is supported by our subgroup analyses demonstrating that BFR training produces a significantly greater hypertrophic effect when compared with LIRT and walk training. However, the HIRT subgroup had a significantly greater increase in muscular hypertrophy than that of the LI-BFR group. This result is masked if looking only at the overall pooled effect. This suggests that HIRT is the best modality of training for increasing muscular hypertrophy.

Although HIRT may result in the greatest increases in muscle CSA overall, this may be unsuitable in frail patients because of the mechanical stress placed on the body. With an aging population, BFR training may become increasingly important in the maintenance of muscular size required to support the functional strength required for activities of daily living.62

Although our study found that BFR training yields greater endurance improvements than endurance training routines alone, this association did not achieve statistical significance. This is in keeping with previous studies which are divided over whether BFR or more classical endurance training regimens produce greater improvements in endurance.20,73 An issue encountered was the lack of research focusing specifically on muscular endurance, such as maximum repetitions. V̇o2 max is a cardiovascular assessment of overall oxygen consumption. Although oxygen is needed for muscular contractions, these data does not provide a direct correlation to muscle endurance. More research should be conducted to investigate whether BFR has a complementary role in muscular endurance training.

Clinically, the above may be of use in the perioperative optimization of patients. Postoperative rehabilitation with HIRT is often not feasible because of the stress of recovery and restrictions regarding weight-bearing. Augmenting rehabilitative LIRT with BFR has the potential to see faster recovery and return to a patient's preoperative functional status. However, the risk of venous thromboembolism (VTE) with BFR training in those already at higher risk after surgery is of great concern. Although Bond et al74 suggest BFR training presents a low risk of VTE, this outcome should be considered significant and any increased risk may be seen as unacceptable to either patients or their clinicians. Alternatively, in the elderly who are more susceptible to muscle atrophy, prehabilitation (enhancing an individual's functional reserve before an upcoming stressor) may be of benefit in promoting faster and greater rehabilitation.75,76 Although this option is limited to elective procedures, it would be more favorable than performing BFR training postoperatively. However, before implementing perioperative BFR protocols, further research is needed to identify the risk to benefit ratio of BFR training in clinical populations.

Ideally, we would have liked to include a greater comparison between both healthy and clinical populations. However, there were limited data available and little overlap in recorded outcomes between these 2 groups, which precluded the proper analysis of the benefits of BFR training in these populations. Future research should be aimed at investigating the use of BFR training in clinical populations.

Strengths

The main strength of this review comes from the methodology used to compile our results. We searched multiple databases, with a repeat search and hand search to include all relevant studies. All screening, extraction, and quality assessment were performed in duplicate with good agreement between authors.

We produced information pertaining to 53 studies comprising 1337 participants, as well as performing in-depth group and subgroup analyses of 33 studies, allowing us to produce a comprehensive review of BFR training over various protocols.

Limitations

One of the main limitations of this systematic review is that many of the pooled estimates demonstrate high heterogeneity. This may be due to variation in training protocols and equipment, and inconsistent reporting of outcomes and differences in patient populations between studies. Furthermore, the response to BFR may be different in the setting of atrophy after injury compared with the normal, uninjured muscle group, in which the goal is improved performance and not just recovery.

High risk of bias was noted in a majority of studies for blinding of participants and assessors to intervention. Segal et al offered the best approach to blinding and was given a low level of bias. We would recommend that other studies adopt the approach by Segal et al of using dummy cuffs, inflated <5 mm Hg, to offer some degree of blinding.58,59

CONCLUSIONS

Blood flow restriction training has demonstrated potential for increasing muscular strength, hypertrophy, and endurance. Comparing occlusive and nonocclusive training, HIRT results in statistically significant larger improvements in muscular strength and hypertrophy. However, subgroup analysis demonstrates that LI-BFR is better when compared with equal low-intensity routines. There was no statistically significant difference between BFR endurance training and endurance training alone. It is unclear whether the statistically significant differences between the 2 groups are clinically significant. BFR may be more appropriate in patients who may not be able to tolerate heavy-load training; however, further investigation of risk versus benefit is needed before clinical application.

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Keywords:

Kaatsu; blood flow restriction; strength training; muscle hypertrophy

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