Effect of training with partial blood flow restriction in older adults : a systematic review

Low-intensity training with blood flow restriction (BFR) has been suggested as an alternative to physical training for older adults. The present study aimed to review the literature regarding the effect of training with BFR for older adults. The search strategy consisted of experimental studies aimed at verifying the effects of training with BFR on any outcome in older adults. An electronic search in PubMed / Medline, Bireme Scielo, Lilacs and Cochrane Library databases, published until December 2015 was conducted. Experimental studies that considered individuals aged 50 years and over published in English or Portuguese, were included. The Downs & Black scale was used to assess the methodological quality of articles. Of the 60 studies, 12 were included in the review. Training with BFR improved body mass, torque and muscle power; functional capacity; bone health; venous compliance; peak oxygen uptake; and blood flow; balance and overall performance. The methodological quality of studies had mean score of 16.2 points (SD = 1.6). The prescription of low-intensity exercises with BFR may be an alternative of training for older adults. However, future studies should address the methodological quality, especially external validity and power, the main gaps in articles reviewed in this study.


INTRODUCTION
The aging process is associated with innumerable unhealthy adaptations in human metabolism, such as cachexia, sarcopenia, increased oxidative stress, systemic inflammation, among others 1,2 .As a consequence, older adults may present worsening quality of life, reduced physical capacity and functional dependence, as well as increased risk of developing chronic non-communicable diseases 1,3 .
On the other hand, physical exercise can reduce the effect of these adaptations, making aging healthier [1][2][3] .The American College of Sports Medicine (ACMS) recommends that older adults should perform 150-300 minutes of aerobic exercise per week and two weekly sessions of strength training, with volumes of 8-12 repetitions 4 .However, many individuals of advanced age may present physical impairment that makes it impossible to perform high training volumes and intensities, leading to adverse effects 5 .
Training with blood flow restriction (BFR) is an alternative, which is characterized by the performance of physical exercises with partial blood flow restriction through the placement of an inflatable band at the root of the limb.This method promises to provide relevant benefits with lower intensities and volumes -aerobic exercise sessions of 20 minutes duration with 50% of maximum aerobic capacity and strength training with intensities from 20% of 1 maximum repetition [6][7][8][9][10][11][12][13] .According to Libardi et al. 13 , the performance of exercises with BFR provides important health advantages for older adults, since they are characterized as exercises with volumes and intensities lower than those recommended by ACMS, therefore causing less mechanical stress, especially in knee joints.
The main findings of the scientific literature have sought to support the use of training with BFR as a method alternative to traditional -conventional training -mainly with samples of healthy and young individuals, although the method is more recommended for populations that present weaknesses that make it impossible to perform exercises with high intensities and volumes, as individuals in rehabilitation and / or older individuals 14 .A meta-analysis conducted by Loenneke et al. 14 included 12 studies, of which only two with a sample composed only of individuals aged 50 years or older.In order to verify the effect of the method on muscle strength and hypertrophy, the authors concluded that low-intensity strength training with BFR promoted significant improvement in muscle strength and hypertrophy -effect size of 0.58 (95% CI: 0.40, 0.76) and 0.39 (95% CI 0.35, 0.43) respectively.
Therefore, since it is an alternative training method that promises to provide important benefits with low intensities, it is fundamental to carry out a review that synthesizes the findings of related studies in a robust way, assuring to adults older and professionals of the area a consistent and nonbiased collection of existing content about the subject.Thus, the present study aimed at reviewing the existing literature regarding the effect of training with BFR on older adults and seniors.

Search strategy
In the systematic review, experimental studies aimed at verifying the effects of training with BFR on any outcome in older adults were selected.An electronic search was carried out in Pubmed/Medline, Bireme, Scielo, Lilacs and Cochrane databases between August 2015 and January 2016.Studies published until December 2015 were also included.
The selection of descriptors used throughout the review process was done according to the Medical Subject Headings (MeSH) and in the specialized literature.The following descriptors were used in the English language: blood flow restriction, vascular occlusion, Kaatsu, resistance training, strength training, weightlifting, low intensity training, walking, cycling, aged, elderly, older.In order to combine descriptors and terms used in the search, logical operators "AND" and "OR" were used.

Eligibility criteria and selection of studies
The review included studies with the following characteristics: experimental studies, full articles published in English or Portuguese and studies with individuals aged 50 years or over.
Two independent reviewers assessed all included studies.In addition, the Downs and Black 15 scale was used to assess the methodological quality of articles.The differences between reviewers were resolved in consensus among them, and there was no need for a third reviewer.The decision to include or exclude studies was initially made based on the analysis of the title, then through the abstract and -finally -the complete manuscript.

Data collection
The information was extracted from each study based on: 1) populationcharacteristics of study participants -age and diagnostic method; 2) intervention -characteristics of the intervention protocol -duration, frequency, intensity, volume and types of exercises, compared to a control group; 3) control -characteristics of the intervention protocol of the comparison group, when there was; and 4) outcome -type of outcome measured.

Analysis of study quality
Initially, a detailed report of scores achieved by studies in each item on the methodological quality scale proposed by Downs and Black 15 -communication, external validity, internal validity (bias and confounding factors) and power -was performed.Then, the percentage of points reached by each article of the maximum possible -31 points -in each item was calculated.At the end, mean and standard deviation (SD) were obtained, as well as the median, amplitude and percentage of points reached.Data were entered in Excel 2013 and analyzed using the Stata 14.0 statistical package.

RESULTS
After searching for all the above mentioned keyword combinations, 73 articles were found, of which 60 were selected, 28 articles in Bireme, 17 in MedLine/PubMed, 15 in Cochranee databases, none in Lilacs and Scielo.Of these, 26 were duplicates, remaining 34 studies to read the titles.After reading, 13 articles were excluded (figure 1).Of the 22 studies qualified for critical reading of abstracts, ten were excluded because subjects were not older adults or because they assessed the acute effect of training with BFR on some outcome.Thus, a total of 12 studies were included in the review [6][7][8][9][10]12,13,[16][17][18][19][20] .
As can be seen in table 1, interventions lasted from 4 17 to 12 weeks 9,10,13 and presented a weekly frequency of two [8][9][10] to five sessions 12 .The sample size ranged from 10 17 to 51 8 individuals.As for the intervention protocol, eight studies 6,10,16,17,19 applied BFR in low-intensity strength exercise, two studies 12,18 in low-intensity walking, and one study 13 in the combination of walking with strength exercises, both of low intensity.
Among the most studied outcomes of chronic responses of training with BFR in older adults, muscle strength was considered in seven articles [7][8][9][10]13,17,19 and muscular hypertrophy in 5 articles 7,9,10,12,13 . The relts found by the reviewed studies indicated that low-intensity training was effective to increase strength and promote muscle hypertrophy when performed with BFR.
Training with BFR performed by older adults and/or seniors also promoted increased muscle torque 12 , improved functional capacity 12 , improved Isometric (11%) and isokinetic (7% -16%) knee extension and flexion torque, transverse musculoskeletal area (5.8% and 5.1% for thigh and leg respectively), as well as muscle mass estimated by ultrasound (6.0% and 10.7% for total and thigh respectively) improved in GBFR (P <0.05), but not in GC.Functional capacity also significantly improved in GBFR (P <0.05).
Iida et al. 18  There were no significant differences between groups in the resting levels of CK, IL-6, IGF-I, IGFBP-3 and Testosterone.In addition, there were no significant changes in the crosssectional area of the muscle, but a trend towards a significant decrease in percentage changes in subcutaneous thigh flexion.

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bone health 16 , increased venous compliance 18 , improved peak oxygen uptake (VO 2 ), increased blood flow 17,18 and improved balance, overall performance, and increased growth hormone concentration 8 .According to criterion proposed by Downs and Black 15 , the average methodological quality score assigned to the articles selected was 16.2 points (SD = 1.6) and the median score was 17 points, with 18 points being the maximum value reached and 13 the minimum, of a maximum total possible of 31 points.Based on this scale, an article with 18 points 17 and seven with 17 points [6][7][8]10,16,19,20 were highlighted. From the quntile categorization of the quality of studies evaluated by the Downs & Black scale, it was observed that all studies are in the intermediate quintile (12.9 to 19.2 points).Table 2 describes in detail the distribution of the methodological quality of studies according to the following items: communication, external validity, internal validity (bias and confounding factors) and power, as well as the percentage of points reached by each article of the total possible in each item.The median percentage of the maximum score among studies was 54.9 points.The lowest scores were on items external validity and power, in which all studies reached 1 point in each of the possible 3 elements in external validity and five in power.

DISCUSSION
Of the 12 studies that fully met the inclusion criteria and were included in this review, seven evaluated the response of low-intensity strength training with BFR on strength and all found a significantly positive effect on the increase of this variable, regardless of whether the weekly frequency was two or three times and the protocol duration of 4 or 12 weeks.In addition, when low-intensity training with BFR was compared with traditional training (high-intensity without BFR), the results were similar between groups 13,19 .Thus, it is possible to affirm that strength training with BFR performed 2 to 3 times a week is effective for improving strength in older adults.Among the factors associated with this improvement, the literature presents neuromuscular adaptations caused by training, such as improvement in neuromuscular and / or nerve coordination, greater recruitment of fast fibers and their motor units and greater muscle activation 10,[21][22][23] .
Regarding muscle mass increase, three studies investigated the effect of strength training with BFR on the cross-sectional area 9,10,13 .The three studies concluded that low-intensity strength training with BFR was effective in improving this variable, with results similar to high-intensity traditional training recommended by ACSM 9,13 , and more effective than low-intensity training without BFR 10 .Previous studies have found that training with BFR optimizes protein synthesis by increasing skeletal muscle myocytes and promoting increased muscle swelling, which, in addition to being associated with protein synthesis, reduces proteolysis 10,24,25 .
In addition to neuromuscular responses, the process of hypertrophy and increased muscle strength promoted by training with BFR is due to metabolic and endocrine responses.The metabolic stress promoted by hypoxia associated with exercise leads to the translocation of type-4 Glucose Transporter (GLUT-4), stimulating the absorption of muscle glucose 26 .In addition, exercise with BFR provides a longer duration of metabolic acidosis, which stimulates the systemic release of the growth hormone (GH) and the consequent increased release of Insulin-1 Growth Factor (IGF-1) 23 .
One study analyzed the response of low-intensity training with BFR on immune system and muscle damage parameters 6 and found no statistically significant changes in creatine kinase (CK) and interleukin-6 (IL-6) serum concentrations.It is important to emphasize that the inflammatory markers analyzed presented values considered normal at baseline, that is, they could not be modified after intervention with physical exercises.The positive point was that training with BFR did not induce additional inflammatory changes.In addition, among the limitations presented by the authors, the lack of control of the participants' diet stood out, a factor that may significantly contribute to the responses in the studied variables, and the last exercise session may have influenced the parameters evaluated, especially CK and IL -6, since blood collection was performed one day after the last exercise session.Depending on the subject's physical fitness level, cytokine and CK levels may remain altered for many hours after the exercise session 6 .Karabulut et al. 16 studied the response of low-intensity training with BFR on bone health 16 .The results indicated that training with BFR showed significant improvements in the concentration of bone health markers when compared to the group that did not exercise (bone alkaline phosphatase -21%, C-Telopeptide -7.6%).Training with BFR can positively affect the secretory function of endothelial cells, which may promote bone remodeling through the synthesis and release of different molecules, such as free radicals and growth factors, which may inhibit osteoclast activity and stimulate osteoblast activity 27,28 .In addition, the increase in muscle strength itself may be associated with improvements in bone health markers 29 .
It is noteworthy that the studies included in the present review presented some common limitations.Although the need for custom prescription of pressure application to obtain adequate BFR according to limb circumference for effective performance during training with BFR 30 is well documented, none of the reviewed studies presented this concern.It is possible that some studies have made this mistake because they were carried out before the publication of the study that standardized the methodology.
The methodological quality presented by studies included in the present review (median score of 17) evaluated through the Dows and Black 15 scale is another important factor that should be discussed.Studies present some restriction mainly on external validity and power (all studies reached only one point of three possible in external validity and one point of five possible in power).Despite the positive results of training with BFR on different outcomes in older adults, especially hypertrophy and muscular strength, the methodological evaluation carried out leads to a cautious interpretation of the findings of studies.However, for allowing the performance of lower intensity exercises and less mechanical stress, especially in the knee joints, training with BFR may provide an interesting advantage for older adults, especially those with joint limitations 13 .

FINAL COMENTS
The results suggest that the prescription of low-intensity exercises with BFR may be an alternative to improve strength, muscle mass, functional capacity, bone health, venous compliance and peak VO 2 without generating excessive muscle damage and inflammatory response in older adults and seniors.However, it is important to note that due to the methodological quality presented by original studies, the findings should be interpreted with caution.Thus, despite the potential benefits of training with BFR in older and seniors, future studies should aim at methodological quality, especially external validity and power, the main gaps in articles reviewed in this study.

vFigure 1 .
Figure 1.Flowchart of the search process of scientific articles.

Table 1 .
Summary of studies on training with partial blood flow restriction Maximum oxygen uptake; LCA -Anterior Cross Ligament.GRFS -Low-intensity force or walk training group with blood flow restriction.GTT -Traditional Training Group -High Intensity Strength Training.GED -Dynamic Balance Training Group.BFR -blood flow restriction of; GC -Control group.

Table 2 .
Methodological quality of studies according to the Downs and Black15 criteria