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

Cardoso, Rodrigo Kohn; Araujo, Aline Machado; Freitas, Matheus Pintanel de; Rombaldi, Airton José

doi:10.5007/1980-0037.2018v20n2p219

Abstract

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.

Key words
Chronic disease; Exercise; Health of the elderly; Muscle strength; Walking

Resumo

O treinamento de baixa intensidade com restrição do fluxo sanguíneo (RFS) tem sido sugerido como alternativa para o treinamento adultos mais velhos e idosos. Assim, o presente estudo objetivou revisar a literatura existente referente ao efeito do treinamento com RFS em adultos mais velhos e idosos. A estratégia de busca consistiu a partir de estudos experimentais que objetivaram verificar os efeitos do treinamento com RFS sobre qualquer desfecho em indivíduos com 50 anos ou mais. Foi realizada busca eletrônica nas bases de dados Pubmed/ Medline, Bireme, Scielo, Lilacs e Cochrane, publicados até dezembro de 2015. Foram incluídos estudos experimentais, publicados em inglês e português, com adultos com 50 anos ou mais. A escala Downs & Black foi utilizada para averiguar a qualidade metodológica dos artigos. Dos 60 estudos encontrados, 12 foram incluídos na revisão. O treinamento com RFS melhorou o grau de força, a massa, o torque e a potência muscular, a capacidade funcional, a saúde óssea, a complacência venosa, o consumo de oxigênio de pico, o fluxo sanguíneo e o equilíbrio e a performance geral. Quanto à qualidade metodológica os estudos apresentaram um escore médio de 16,2 pontos (DP=1,6). A prescrição de exercícios de baixa intensidade com RFS pode ser uma alternativa para o treinamento de adultos mais velhos e idosos. Porém, futuros estudos devem atentem para a qualidade metodológica, especialmente validade externa e poder, principais lacunas apresentadas pelos estudos revisados.

Palavras-chave
Caminhada; Doença crônica; Exercício; Força muscular; Saúde do idoso

INTRODUCTION

The aging process is associated with innumerable unhealthy adaptations in human metabolism, such as cachexia, sarcopenia, increased oxidative stress, systemic inflammation, among others¹^,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 diseases¹^,³.

On the other hand, physical exercise can reduce the effect of these adaptations, making aging healthier¹^-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 repetitions⁴. However, many individuals of advanced age may present physical impairment that makes it impossible to perform high training volumes and intensities, leading to adverse effects⁵.

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 repetition⁶^-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 individuals¹⁴. 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 non-biased 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.

METHODOLOGICAL PROCEDURES

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 Black¹⁵ 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) population - characteristics 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 Black¹⁵ - 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).

Figure 1
Flowchart of the search process of scientific articles

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 review⁶^-¹⁰^,¹²^,¹³^,¹⁶^-²⁰.

As can be seen in table 1, interventions lasted from 4¹⁷ to 12 weeks⁹^,¹⁰^,¹³ and presented a weekly frequency of two⁸^-¹⁰ to five sessions¹². The sample size ranged from 10¹⁷ to 51⁸ individuals. As for the intervention protocol, eight studies⁶^,¹⁰^,¹⁶^,¹⁷^,¹⁹ applied BFR in low-intensity strength exercise, two studies¹²^,¹⁸ in low-intensity walking, and one study¹³ in the combination of walking with strength exercises, both of low intensity.

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Table 1
Summary of studies on training with partial blood flow restriction

Among the most studied outcomes of chronic responses of training with BFR in older adults, muscle strength was considered in seven articles⁷^-¹⁰^,¹³^,¹⁷^,¹⁹ and muscular hypertrophy in 5 articles⁷^,⁹^,¹⁰^,¹²^,¹³. The results 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 torque¹², improved functional capacity¹², improved bone health¹⁶, increased venous compliance¹⁸, improved peak oxygen uptake (VO₂), increased blood flow¹⁷^,¹⁸ and improved balance, overall performance, and increased growth hormone concentration⁸.

According to criterion proposed by Downs and Black¹⁵, 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 points¹⁷ and seven with 17 points⁶^-⁸^,¹⁰^,¹⁶^,¹⁹^,²⁰ were highlighted. From the quintile 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.

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

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 groups¹³^,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 activation¹⁰^,²¹^-²³.

Regarding muscle mass increase, three studies investigated the effect of strength training with BFR on the cross-sectional area⁹^,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 ACSM⁹^,¹³, and more effective than low-intensity training without BFR¹⁰. 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 proteolysis¹⁰^,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 parameters⁶ 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 session⁶.

Karabulut et al.¹⁶ studied the response of low-intensity training with BFR on bone health¹⁶. 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 activity²⁷^,²⁸. In addition, the increase in muscle strength itself may be associated with improvements in bone health markers²⁹.

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 BFR³⁰ 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 Black¹⁵ 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 limitations¹³.

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 VO₂ 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.

REFERENCES

¹ Singh M. Exercise and aging. Clin Geriatr Med 2004;20(2):201-21.
² Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: a “set up” for vascular disease. Circulation 2003;107(1):139-46.
³ Paterson D. Physical activity, fitness, and gender in relation to morbidity, survival, quality of life, and independence in older age. In: Shephard R, editor. Gender, Physical Activity, and Aging. Boca Raton (FL): CRC Press 2002; 99-120.
⁴ Chodzko-Zajko W, Proctor DN, Fiatarone SM, Minson CT, Nigg CR, Salem GJ, et al. Exercise and Physical Activity for Older Adults. Med Sci Sports Exerc 2009;41(7):1510-30.
⁵ Haykowsky MJ, Findlay JM, Ignaszewski AP. Aneurysmal subarachnoid hemorrhage associated with weight training: three case reports. Clin J Sports Med 1996; 6(1):52-5.
⁶ Karabulut M, Sherk VD, Bemben DA, Bemben MG. Inflammation marker, damage marker and anabolic hormone responses to resistance training with vascular restriction in older males. Clin Physiol Funct Imaging 2013;33(5):393-9.
⁷ Thiebaud RS, Loenneke JP, Fahs CA, Rossow LM, Kim D, Abe T, et al. The effects of elastic band resistance training combined with blood flow restriction on strength, total bone-free lean body mass and muscle thickness in postmenopausal women. Clin Physiol Funct Imaging 2013;33(5):344-52.
⁸ Yokokawa Y, Hongo M, Urayama H, Nishimura T, Kai I. Effects of low intensity resistance exercise with vascular occlusion on physical function in healthy elderly people. Biosci Trends 2008;2(3):117-23.
⁹ Vechin FC, Libardi CA, Conceicão MS, Damas FR, Lixandrão ME, Berton RP, Tricoli VA. Comparisons between low-intensity resistance training with blood flowrestriction and high-intensity resistance training on quadriceps muscle mass and strength in elderly. J Strength Cond Res 2015;29(4):1071-76.
¹⁰ Yasuda T, Fukumura K, Uchida Y, Koshi H, Iida H, Masamune K, et al. Effects of low-load, elastic band resistance training combined with blood flow restriction on muscle size and arterial stiffness in older adults. J Gerontol A Biol Sci Med Sci 2015;70(8):950-8.
¹¹ Loenneke JP, Thiebaud RS, Abe T,Bemben MG,. Blood flow restriction pressure recommendations: the hormesis hypothesis. Med Hypotheses 2014;82(5);623-6.
¹² Abe T, Sakamaki M, Fujita S, Ozaki H, Sugaya M, Sato Y, et al. Effects of low-intensity walk training with restricted leg blood flow on muscle strength and aerobiccapacity in older adults. J Geriatr Phys Ther 2010;33(1):34-40.
¹³ Libardi CA, Chacon-Mikahil MPT, Cavaglieri CR, Tricoli V, Roschel H, VechinFC, et al. Effect of concurrent training with blood flow restriction in the elderly. Int J Sports Med 2015;36(5):395-9.
¹⁴ Loenneke JP, Wilson JM, Marín PJ, Zourdos MC, Bemben MG. Low intensity blood flow restriction training: A meta-analysis. Eur J Appl Physiol2012;112(5):1849–59.
¹⁵ Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52(6):377-84.
¹⁶ Karabulut M, Bemben DA, Sherk VD, Anderson MA, Abe T, Bemben MG. Effects of high-intensity resistance training and low-intensity resistance training with vascular restriction on bone markers in older men. Eur J Appl Physiol 2011;108(11):1659-67.
¹⁷ Patterson SD, Ferguson RA. Enhancing strength and postocclusive calf blood flow in older people with training with blood-flow restriction. J Aging Phys Act 2011;19(3):201-13.
¹⁸ Iida H, Nakajima T, Kurano M, Yasuda T, Sakamaki M, Sato Y, et al. Effects of walking with blood flow restriction on limb venous compliance in elderly subjects. Clin Physiol Funct Imaging 2011;31(6):472-6.
¹⁹ Karabulut M, Abe T, Sato Y, Bemben MG. The effects of low-intensity resistance training with vascular restriction on leg muscle strength in older men. Eur J Appl Physiol 2010;108(1):147-55.
²⁰ Shimizu R, Hotta K, Yamamoto S, Matsumoto T, Kamiya K, Kato M, et al. Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people. Eur J Appl Physiol 2016;116(4):749-57.
²¹ Karabulut M, Abe T, Sato Y, Bemben MG. Overview of neuromuscular adaptationsof skeletal muscle to KAATSU training. Int J Kaatsu Train Res 2007; 3(1):1–9.
²² Moritani T, Sherman WM, Shibata M, Matsumoto T, Shinohara M. Oxygen availability and motor unit activity in humans. Eur J Appl Physiol Occup Physiol 1992; 64(6):552–6.
²³ Pope ZK, Willardson JM, Schoenfeld. Exercise and blood flow restriction. JStrength Cond Res 2013; 27(10):2914-26.
²⁴ Keller U, Szinnai G, Bilz S, Berneis K. Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health. Eur J Clin Nutr 2003;57(2):69–74.
²⁵ Millar ID, Barber MC, Lomax MA, Travers MT, Shennan DB. Mammary proteinsynthesis is acutely regulated by the cellular hydration state. Biochem Biophys Res Commun 1997; 230(2):351–5.
²⁶ Fluckey, JD, Ploug, T, and Galbo, H. Mechanisms associated with hypoxia and contraction-mediated glucose transport in muscle are fibre-dependent. Acta PhysiolScand 1999;167(1):83–7.
²⁷ Parfitt AM. The mechanism of coupling: a role for the vasculature. Bone2000;26(4):319–23.
²⁸ McCarthy I. The physiology of bone blood flow: a review. J Bone Joint Surg Am 2006;88(3):4–9.
²⁹ Frost HM. From Wolff’s law to the Utah paradigm: insights about bone physiologyand its clinical applications. Anat Rec 2001;262(4):398–419.
³⁰ Loenneke JP, Kim D, Fahs CA, Thiebaud RS, Abe T, Larson RD, et al. Effects of exercise with and without different degrees of blood flow restriction on torque and muscle activation. Muscle Nerve 2015;51(5):713-21.

Publication Dates

Publication in this collection
Mar-Apr 2018

History

Received
14 Apr 2017
Accepted
12 Dec 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

[1] ¹ Singh M. Exercise and aging. Clin Geriatr Med 2004;20(2):201-21.

[2] ² Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: a “set up” for vascular disease. Circulation 2003;107(1):139-46.

[3] ³ Paterson D. Physical activity, fitness, and gender in relation to morbidity, survival, quality of life, and independence in older age. In: Shephard R, editor. Gender, Physical Activity, and Aging. Boca Raton (FL): CRC Press 2002; 99-120.

[4] ⁴ Chodzko-Zajko W, Proctor DN, Fiatarone SM, Minson CT, Nigg CR, Salem GJ, et al. Exercise and Physical Activity for Older Adults. Med Sci Sports Exerc 2009;41(7):1510-30.

[5] ⁵ Haykowsky MJ, Findlay JM, Ignaszewski AP. Aneurysmal subarachnoid hemorrhage associated with weight training: three case reports. Clin J Sports Med 1996; 6(1):52-5.

[6] ⁶ Karabulut M, Sherk VD, Bemben DA, Bemben MG. Inflammation marker, damage marker and anabolic hormone responses to resistance training with vascular restriction in older males. Clin Physiol Funct Imaging 2013;33(5):393-9.

[7] ⁷ Thiebaud RS, Loenneke JP, Fahs CA, Rossow LM, Kim D, Abe T, et al. The effects of elastic band resistance training combined with blood flow restriction on strength, total bone-free lean body mass and muscle thickness in postmenopausal women. Clin Physiol Funct Imaging 2013;33(5):344-52.

[8] ⁸ Yokokawa Y, Hongo M, Urayama H, Nishimura T, Kai I. Effects of low intensity resistance exercise with vascular occlusion on physical function in healthy elderly people. Biosci Trends 2008;2(3):117-23.

[9] ⁹ Vechin FC, Libardi CA, Conceicão MS, Damas FR, Lixandrão ME, Berton RP, Tricoli VA. Comparisons between low-intensity resistance training with blood flowrestriction and high-intensity resistance training on quadriceps muscle mass and strength in elderly. J Strength Cond Res 2015;29(4):1071-76.

[10] ¹⁰ Yasuda T, Fukumura K, Uchida Y, Koshi H, Iida H, Masamune K, et al. Effects of low-load, elastic band resistance training combined with blood flow restriction on muscle size and arterial stiffness in older adults. J Gerontol A Biol Sci Med Sci 2015;70(8):950-8.

[11] ¹¹ Loenneke JP, Thiebaud RS, Abe T,Bemben MG,. Blood flow restriction pressure recommendations: the hormesis hypothesis. Med Hypotheses 2014;82(5);623-6.

[12] ¹² Abe T, Sakamaki M, Fujita S, Ozaki H, Sugaya M, Sato Y, et al. Effects of low-intensity walk training with restricted leg blood flow on muscle strength and aerobiccapacity in older adults. J Geriatr Phys Ther 2010;33(1):34-40.

[13] ¹³ Libardi CA, Chacon-Mikahil MPT, Cavaglieri CR, Tricoli V, Roschel H, VechinFC, et al. Effect of concurrent training with blood flow restriction in the elderly. Int J Sports Med 2015;36(5):395-9.

[14] ¹⁴ Loenneke JP, Wilson JM, Marín PJ, Zourdos MC, Bemben MG. Low intensity blood flow restriction training: A meta-analysis. Eur J Appl Physiol2012;112(5):1849–59.

[15] ¹⁵ Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52(6):377-84.

[16] ¹⁶ Karabulut M, Bemben DA, Sherk VD, Anderson MA, Abe T, Bemben MG. Effects of high-intensity resistance training and low-intensity resistance training with vascular restriction on bone markers in older men. Eur J Appl Physiol 2011;108(11):1659-67.

[17] ¹⁷ Patterson SD, Ferguson RA. Enhancing strength and postocclusive calf blood flow in older people with training with blood-flow restriction. J Aging Phys Act 2011;19(3):201-13.

[18] ¹⁸ Iida H, Nakajima T, Kurano M, Yasuda T, Sakamaki M, Sato Y, et al. Effects of walking with blood flow restriction on limb venous compliance in elderly subjects. Clin Physiol Funct Imaging 2011;31(6):472-6.

[19] ¹⁹ Karabulut M, Abe T, Sato Y, Bemben MG. The effects of low-intensity resistance training with vascular restriction on leg muscle strength in older men. Eur J Appl Physiol 2010;108(1):147-55.

[20] ²⁰ Shimizu R, Hotta K, Yamamoto S, Matsumoto T, Kamiya K, Kato M, et al. Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people. Eur J Appl Physiol 2016;116(4):749-57.

[21] ²¹ Karabulut M, Abe T, Sato Y, Bemben MG. Overview of neuromuscular adaptationsof skeletal muscle to KAATSU training. Int J Kaatsu Train Res 2007; 3(1):1–9.

[22] ²² Moritani T, Sherman WM, Shibata M, Matsumoto T, Shinohara M. Oxygen availability and motor unit activity in humans. Eur J Appl Physiol Occup Physiol 1992; 64(6):552–6.

[23] ²³ Pope ZK, Willardson JM, Schoenfeld. Exercise and blood flow restriction. JStrength Cond Res 2013; 27(10):2914-26.

[24] ²⁴ Keller U, Szinnai G, Bilz S, Berneis K. Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health. Eur J Clin Nutr 2003;57(2):69–74.

[25] ²⁵ Millar ID, Barber MC, Lomax MA, Travers MT, Shennan DB. Mammary proteinsynthesis is acutely regulated by the cellular hydration state. Biochem Biophys Res Commun 1997; 230(2):351–5.

[26] ²⁶ Fluckey, JD, Ploug, T, and Galbo, H. Mechanisms associated with hypoxia and contraction-mediated glucose transport in muscle are fibre-dependent. Acta PhysiolScand 1999;167(1):83–7.

[27] ²⁷ Parfitt AM. The mechanism of coupling: a role for the vasculature. Bone2000;26(4):319–23.

[28] ²⁸ McCarthy I. The physiology of bone blood flow: a review. J Bone Joint Surg Am 2006;88(3):4–9.

[29] ²⁹ Frost HM. From Wolff’s law to the Utah paradigm: insights about bone physiologyand its clinical applications. Anat Rec 2001;262(4):398–419.

[30] ³⁰ Loenneke JP, Kim D, Fahs CA, Thiebaud RS, Abe T, Larson RD, et al. Effects of exercise with and without different degrees of blood flow restriction on torque and muscle activation. Muscle Nerve 2015;51(5):713-21.

Author	Sample	Aim	Intervention	Main results
Abe et al.¹²	19 individuals (60-78 years)	Investigate the effects of walking training with BFR on muscle size, strength and functionality	GBFR: walking with BFR; GC - walking without BFR.	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	16 women (59 - 78 years)	Examine the influence of walking with BFR on venous compliance in older women.	GBFR: Walking with BFR; GC: Hiking without BRF.	Venous compliance (Pre: 0.0518 ± 0.0084, post: 0.0619 ± 0.0150 ml / 100 ml / mmHg (P <0.05) and maximum venous flow (pre: 55.3 ± 15.6 , post: 67.1 ± 18.9 ml / 100 ml / min (P <0.01) increased significantly in GBFR but not in GC.
Karabulut et al.¹⁹	37 men (50 - 64 years)	Compare the effect of two types of strength training on the adaptation of muscular strength in older men	GTT - High intensity strength training without BFR; GBFR - Low intensity strength training with BFR; GC - No exercise.	GTT and GBFR groups showed significantly greater strength improvements in the legpress exercise when compared to GC (p <0.05), with similar gains between GTT and GBFR. In the leg extension exercise, GTT presented significantly greater force gain than GBFR (p <0.05).
Karabulut et al.¹⁶	37 men (50 - 64 years)	Compare the effect of different types of strength training on the concentration of bone markers in older men	GTT - High intensity strength training without RFS; GBFR - Low intensity strength training with BFR; GC - No exercise.	A significant effect was detected on bone alkaline phosphatase in exercise groups (p <0.05), 21%, 23% and 4.7% for LIBF, HIT and Gc respectively. HIT and LIBFR groups presented significantly greater gains when compared to GC (p <0.05), except for the leg extension exercise (HIT> LIBFR> GC, p <0.05).
Karabulut et al.⁶	37 men (50 - 64 years)	Compare the effect of different types of strength training on anabolic hormones, damage markers and inflammatory markers in older men.	GTT - High intensity strength training without BFR; GBFR - Low intensity strength training with BFR; GC - No exercise.	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.
Libardi et al.¹³	25 individuals (64 ± 4.1 years)	Investigate the effects of concurrent training with BFR and non-BFR on aerobic fitness, muscle mass and muscle strength in a cut of older individuals.	GTT: high intensity strength training without BFR (2 days / week). GBFR: low intensity strength training with BFR (2 days / wk)	GTT and GRFS showed similar increases in thigh muscle transverse area in the post-test (7.3% and 7.6%, respectively), maximal strength (38.1% and 35.4%, respectively) and VO2max (9.5%, P = 0.04, 10.3%, P = 0.02, respectively).
Patterson et al.¹⁷	10 individuals (62-73 years)	Check strength training response with and without BFR on calf strength	Low intensity force training. One leg with BFR and another without.	Maximum strength, maximal voluntary isometric contraction, and isokinetic strength at 0.52 rad / s increased more after training with BFR than without BFR Peak blood flow post BFR increased after training with BFR, compared to no change after training without BFR.
Thiebaud et al.⁷	14 women (61±5 years)	Check the effects of different strength training intensities with and without BFR on strength and muscle mass.	GBFR: Low intensity strength training with BFR; GC: Low intensity strength training without BFR.	Maximum seated bench press (P = 0.01), shoulder pressure (P = 0.02) and sitting row (P = 0.01) force increased significantly, but no differences were found between groups. Only greater thickness of the pectoral muscle was found (P = 0.04).
Vechin et al.⁹	23 older adults (64.04±3.81 years)	Compare the effects of different types of training on quadriceps muscle strength and muscle mass in the elderly.	GTT: High intensity strength training without BFR; GRFS: Low intensity strength training with BFR; GC: without exercise.	Both training protocols were effective in increasing maximal strength in legpress (GTT: 54%, p <0.001; GRFS: 17%, p = 0.067) and quadriceps cross-sectional area (GTT: 7.9%, p <0.001 ; GRFS: 6.6%, p <0.001); however, traditional high-intensity training seems to induce greater strength gain.
Yasuda et al.¹⁰	17 individuals (61-85 years)	Examine the effect of strength training with BFR on muscle size and arterial stiffness.	GC: Low intensity strength training without BFR; GRFS: Low intensity strength training with BFR;	Flexor (17.6%) and elbow extensors (17.4%) cross-sectional area increased, as well as maximal isometric voluntary contraction of flexors (7.8%) and elbow extensors (16.1%) improved in GRFS, but not in GTT. There were no changes in the ankle cardiovascular index and ankle-brachial pressure index in both groups.
Yokokawa et al.⁸	51 individuals (65 years or more).	To compare the effects of two types of training in the elderly.	GRFS: Low intensity strength training with BFR; GED: Dynamic balance training.	Improvements were found in overall performance and balance after training programs, but there were no differences between groups. Muscle strength in the lower limbs increased significantly in GRFS, but not in GED. Growth hormone concentration increased significantly in GRFS.
Shimizu et al.²⁰	40 individuals (71 ± 4 years)	Investigate the effects of training with BFR on endothelial function and circulation in the elderly	GRFS: Low intensity strength training with BFR; GC: Low intensity strength training without BFR.	The lactate, norepinephrine and growth hormone concentrations increased significantly more in GRFS than in GC. GRFS showed significant improvement in endothelial function and peripheral blood circulation. There was no difference in muscle strength between groups, but both increased the strength of the lower limbs.

Study	Communication	External validity	VI (bias)	VI (confounding factor)	Power	Total	Percentage
Abe et al.¹²	6	1	3	4	1	15	48.4
Iida et al.²⁴	5	1	3	3	1	13	41.2
Karabulut et al.¹⁹	7	1	3	5	1	17	54.9
Karabulut et al.¹⁶	7	1	3	5	1	17	54.9
Karabulut et al.⁶	7	1	3	5	1	17	54.9
Shimizu et al.²⁰	7	1	4	4	1	17	54.9
Yokokawa et al.⁸	8	1	3	4	1	17	54.9
Yasuda et al.¹⁰	7	1	4	4	1	17	54.9
Vechin et al.⁹	6	1	4	4	1	16	51.6
Thiebaud et al.⁷	7	1	3	5	1	17	54.9
Patterson et al.²³	7	1	4	5	1	18	58.1
Libardi et al.¹³	4	1	3	4	1	13	41.2