Effect of Blood Flow Restriction Technique on Delayed Onset Muscle Soreness: A Systematic Review

Background and Objectives: The effect of the blood flow restriction technique (BFR) on delayed onset muscular soreness (DOMS) symptoms remains unclear. Since there is no consensus in the literature, the aim of the present study is to systematically identify and appraise the available evidence on the effects of the BFR technique on DOMS, in healthy subjects. Materials and Methods: Computerized literature search in the databases Pubmed, Google Scholar, EBSCO, Cochrane and PEDro to identify randomized controlled trials that assessed the effects of blood flow restriction on delayed onset muscular soreness symptoms. Results: Eight trials met the eligibility criteria and were included in this review, presenting the results of 118 participants, with a mean methodological rating of 6/10 on the PEDro scale. Conclusions: So far, there is not enough evidence to confirm or refute the influence of BFR on DOMS, and more studies with a good methodological basis are needed, in larger samples, to establish protocols and parameters of exercise and intervention. Data analysis suggests a tendency toward the proinflammatory effect of BFR during high restrictive pressures combined with eccentric exercises, while postconditioning BFR seems to have a protective effect on DOMS. Prospero ID record: 345457, title registration: “Effect of Blood Flow Restriction Technique on the Prevention of Delayed Onset Muscle Soreness: A Systematic Review”.


Introduction
DOMS is defined as a functional muscle injury due to overexertion [1], more specifically, it is a generalized muscle pain following unaccustomed, eccentric deceleration movements. It has been classified as a type 1B sports' muscle injury, by the Munich consensus statement [2]. It is usually caused by eccentric muscle contractions that require the stretching of muscle fibers or the practice of unusual and/or intensive exercises [3]. Symptoms include acute inflammatory pain, namely at rest, hours after the onset of activity [2]. DOMS results from the expression of a complex pathophysiological mechanism [4] whose exact cause is not well understood but is believed to involve inflammatory reaction or even muscle damage [5].
In 1977, a document from V. W. Abraham [6] evaluated DOMS from three different perspectives, surface electromyography to evaluate muscle spasm, presence of myoglobinuria to evaluate the possibility of muscle cell damage, while the ratio of hydroxyproline/creatinine (OHP/Cr) in 24 h urine collection was used as a marker for connective tissue involvement, and concluded that the observations supported the concept that exerciseinduced soreness may be related to disruption of the connective tissue elements in the muscle and/or their attachments. Furthermore, these changes are thought to be due to

Materials and Methods
The research was conducted using the PICO strategy [27] with a defined population: adults, healthy, without disease or musculoskeletal injuries, an intervention with BFR or TF techniques combined with exercise, a comparison including the same exercises but without BFR or TF, and typical outcomes of DOMS. This review followed the recommendations of PRISMA (Preferred Reporting Items for Systematic Reviews) [28].
In the present review, a computerized literature search was performed by two independent researchers, with the following primary keywords: "tissue flossing", "restricted blood flow", "delayed onset muscle soreness", "DOMS" using logical operators (AND and OR) making the following combination ("tissue flossing" OR "blood flow restriction" OR kaatsu) AND ("DOMS" OR "delayed onset muscle soreness"), from inception till December 2021. The included databases were Pubmed, Google Scholar, EBSCO, Cochrane and PEDro. The final selection of articles met the following eligibility criteria: (1) Randomized controlled trials; (2) With no language restriction; (3) Studies evaluating the effects of the BFR technique with cuff occlusion or floss band on the prevention of DOMS; (4) Studies conducted in trained or untrained adult individuals who did not present pathologies or musculoskeletal injuries; (5) Studies whose experimental group has the BFR technique and whose control group does the same training without BFR application; (6) Studies whose application of BFR technique is carried out during or after the end of training; (7) Intervention with a training protocol of endurance, strength or aerobic training; (8) Studies evaluating DOMS at the beginning and several days after exercise, including at least one of these result measures: pain scales, namely the visual analog pain scale (VAS), DOMS scales such as the Likert Scale of Muscle Soreness, measurements of algometry (i.e., pressure pain threshold), measurements of the activity of blood marshes such as CK or LDH, evaluation of muscle strength and function, such as the maximum voluntary isometric contraction, evaluation of edema (e.g., limb girth measurement) and range of motion evaluation. Articles were included from inception to date. To determine the eligibility or exclusion of each study, the titles, and abstracts of all articles and, in case of doubt, the full text was red.
The methodological quality was evaluated by two independent researchers, using the Physical Evidence Database scoring scale (PEDro) whose application allows quick and effective identification of studies that may have internal validity (criteria 2-9) and sufficient statistical information to perform an interpretation of its results (criteria [10][11]. The final score is attributed by the sum of the number of criteria classified as satisfactory between 2 and 11, and criterion 1, relative to external validity, is not considered in the calculation. The score can vary between 0 and 10 points and will allow us to have a careful evaluation of randomized controlled studies to include in the performance of systematic reviews [29].

Results
During the research carried out in the different databases, a total of 309 articles were found, and this total was reduced to 70 after reading of the titles, and then to 31 postreading of the abstract. Of these 31 articles, after reading the full text, 8 articles were selected ( Figure 1).

Evaluation of Methodological Quality
The studies present methodological quality with an arithmetic mean of 5.88 out of 10 on the PEDro scale, the result of the evaluation of two independent raters (Table 1).
Brandner e Warmington [30], aimed to determine the perceptual responses to resistance exercise with heavy loads (80% of 1 repetition maximum [1RM]), light loads (20% 1RM), or light loads in combination with BFR. Seventeen healthy untrained males participated in this randomized cross-over study. After four sets of an elbow-flexion exercise,

Evaluation of Methodological Quality
The studies present methodological quality with an arithmetic mean of 5.88 out of 10 on the PEDro scale, the result of the evaluation of two independent raters (Table 1).
Curty et al. [31], aimed to evaluate the acute effects of high-intensity eccentric exercise combined with BFR on muscle damage markers, perceptual and cardiovascular responses. Nine healthy men underwent unilateral elbow extension in two conditions: without and with BFR. The protocol corresponded to three sets of 10 repetitions with 130% of maximal strength (1RM).
Freitas et al. [32], investigated if resistance exercise performed at differing Arterial Occlusion Pressures causes oxidative stress and muscle damage. Twelve males completed 4 sets of 10 repetitions of knee extension at 20% of 1RM, with 30 s rest intervals between sets, that varied only in the amount of restriction pressure applied.
Page, Swan e Patterson [33], examined the effectiveness of intermittent lower limb occlusion in augmenting recovery from exercise-induced muscle damage in physically active males. The sample consisted of sixteen healthy recreationally active male participants who were randomly assigned to an intermittent occlusion (n = 8) or control (sham; n = 8) group and the protocol consisted of 100 drop-jumps.
Penailillo et al. [34], compared the effects of eccentric cycling and eccentric cycling with blood flow restriction on the changes in cardio-metabolic demand and indirect markers of muscle damage in 21 healthy men, that were randomly allocated into two groups.
Prill, Schulz and Michel [19], investigated if BFR applied to the upper limb, after exercise, would reduce the perception of DOMS, for this, 17 university students underwent an upper limb exertion program and had one of their upper limbs treated afterward.
Thiebaud et al. [35], studied the amount of muscle damage after low-intensity eccentric contractions with blood flow restriction. For this, the authors have compared low-intensity eccentric contractions of the elbow flexors with and without BFR for changes in indirect markers of muscle damage. Nine untrained young men performed the exercises with one arm assigned to BFR and the other without BFR.
Wernbom et al. [36], aimed to investigate muscle activity and endurance during fatiguing low-intensity dynamic knee extension exercises with and without blood flow restriction. For this, eleven healthy subjects with strength training experience performed three sets of unilateral knee extensions till concentric torque failure at 30% of the one repetition maximum. According to the reported protocol, one leg was randomized to exercise with cuff occlusion and the other leg to exercise without occlusion.

Discussion
The studies included in the present review seem to be clustered into three main categories, those in favor of a pro-inflammatory effect and theoretically greater muscular adaptations to exercise, those in favor of an anti-inflammatory effect, and the ones that advocate no effect of the technique.
Studies in favor of a pro-inflammatory response of the BFR on DOMS. Brandner and Warmington [30] and Penailillo et al. [34], showed a significant increase in different parameters of DOMS in their experimental groups with BFR application compared to the control group. Furthermore, the cross-over study by Brandner and Warmington [30] suggests that the resistance exercise with BFR in elbow flexors, either with a heavy load (80% of 1RM) or with a light load (20% of 1RM), results in greater indicis of DOMS than the exercise without BFR. It was also observed that induced DOMS is higher when BFR is applied with high intermittent pressure than with low continuous pressure, suggesting that high restrictive pressures on muscle tissue can promote the appearance of DOMS. The study by Penailillo et al. [34], using the eccentric cycle ergometer at 60 rpm, combined or not with BFR, did not show significant differences in the level of the pressure pain threshold between the two groups, but there was a later recovery in the initial pain threshold on the EG than in the CG, demonstrating a tendency to induce higher DOMS in exercise under BFR. Moreover, they also observed a slower recovery to the initial levels of MVC and the initial level of muscle pain in the exercise group combined with BFR, when compared to the condition without BFR [30,34].
In these studies that support the pro-inflammatory effect of the BFR technique, the applied pressure was always adapted to each of the participants, thus allowing the achievement of higher levels of accuracy both in the protocol and in the results of the studies [30,34]. In the study by Brandner and Warmington [30], the pressure was defined from 80 to 130% of PSS (i.e., a pressure of 93 ± 2 mmHg at 152 ± 3 mmHg) and Penailillo et al. [34] defined a pressure of approximately 60% of the arterial occlusion (i.e., on average 192 ± 24 mmHg), estimated from the thigh girth of each participant. Despite having different protocols, types of exercises, and BFR pressures, the results of these studies show that eccentric exercise with BFR induces additional effects of mechanical and metabolic stress that induce higher levels of inflammation and thus increase the production of reactive oxygen species during exercise [37], with induction of higher Levels of DOMS and recovery times.
In addition, despite the BFR technique promoting more DOMS, it has been shown that its additional effects of mechanical and metabolic stress may have advantages, since they constitute the first responsible factors for muscle hypertrophy, by demonstrating that the BFR technique promotes strength and muscle mass gain [38].
Studies in favor of an anti-inflammatory effect of the BFR on DOMS. Concurrently, Wernbom [36], Page, Swan and Patterson [33], and Prill, Schulz and Michel [19] found significant results among the experimental and control groups showing a decrease in DOMS due to the application of the BFR technique, namely at the level of the evaluated parameters like pain (in the three studies) and muscle strength and CK levels [33]. The decrease in DOMS suggests a reduction in the inflammatory response (by decreasing the influx of inflammatory mediators) allowed by the BFR technique, thus leading to the reduction of muscle edema and intramuscular pressure, which decreases the sensitivity and stimulation of nociceptors, potentially reducing the sensations of pain, stiffness, and myalgias [39]. Despite having similar conclusions, these three studies show some differences, particularly in the time of technical performance. Prill, Schulz and Michel [19], and Page, Swan and Patterson [33] induced BFR after exercise, called the ischemic postconditioning process, and not during exercise as in the Wernbom study [36]. There are also differences in the exercise protocols: 100 drop-jumps [33], different exercises for biceps to failure [19], or unilateral knee extensions to 30% of 1RM until failure [36]. All studies with anti-inflammatory results used different BFR pressures: 100 mmHg [19,36], elastic band elongation of 50 to 75% of maximum elongation [17], and 220 mmHg [33] that are already predefined, i.e., they are not chosen specifically for the participant.
Besides, Curty et al. [31], also showed that the BFR technique combined with exercise can have preventive effects on DOMS with faster recovery with BFR than without. In this study, the participants had a limb belonging to the experimental group and the contralateral limb belonging to the control group (30 min between the two groups), the exercise consisted of 3 sets of 10 unilateral eccentric extensions of the elbow, at 130% of 1 RM, with 1 min rest between trials. The BFR was used at 80% of arterial occlusion. There were no significant differences between the two groups both in terms of edema and range of motion. However, ROM in the experimental group returned to the initial degree earlier (after 24 h) than in the control group (after 48 h). A significant difference was also found in the experimental group at the level of pain (evaluated by NPS) because at 48 h it presented less DOMS than in the exercise group.
Studies that do not support either the anti-inflammatory effect or the pro-inflammatory effect of the BFR technique [32,35]. In the study by Freitas et al. [32], participants performed four equal training protocols (4 series of 10 unilateral knee extension repetitions with 30 s of rest) each week with different BFR pressures but specific for each participant: without BFR, 50% of the total AOP (66.58 ± 9.72 mmHg), 75% (99.25 ± 14.95 mmHg) and 100% (129.50 ± 18.73). In this study, the maximum isometric contraction was measured at 1 h, 24 h, and 48 h post-exercise and there was no decrease in isometric strength at any time, regardless of the applied pressure. In addition, there was no increase in DOMS either, for any of the exercise conditions in this study. CK and LDH levels were also measured as indirect biomarkers of muscle damage. Clarkson and Hubal [40] stated that CK levels should increase more than 100% after resistance exercise compared to their baseline levels and that they remain elevated for several days after resistance exercise. However, no significant increases in baseline values in CK and LDH levels were observed over time for any of the conditions tested. Although LDH levels have increased significantly for all conditions 48 h post-exercise compared to 24 h post-exercise, this difference is probably due to normal daily variations in blood LDH levels after performing an exercise. This fact is corroborated by the absence of significant difference between the conditions tested at the various moments after the exercise. In addition, it is important to highlight that the authors outlined the study so that the experimental group completed the repetitions until muscle failure while the control group only completed the same number of repetitions as the experimental group without reaching muscle failure since they were not subjected to BFR. These facts could be pointed out as potential study bias.
In addition, Thiebaud et al. [35], performed a study in which the participants had one control upper limb (without BFR) and another experimental limb (with BFR) (30 min of intervals between the two groups) and performed an eccentric contraction protocol of the biceps at 30% of 1RM, 4 series of 30/15/15/15 repetitions with 30 s of rest. The BFR technique was performed throughout the exercise, with a predefined pressure of 35 mmHg initially, until gradually reaching a final pressure of 120 mmHg. In this study, no significant difference was found in the different parameters evaluated, only a decrease in strength of 7% was shown after exercise. Thus, despite having very different exercise protocols and BFR, no significant differences were found between the experimental and control groups in any of the evaluated parameters: i.e., pain, CK and/or LDH levels, muscle strength, ROM, and edema. Thus, both concluded that the exercise combined with BFR neither promotes nor decreases muscle damage and consequently DOMS.
Loenneke, Thiebaud and Abe [41], who examined the mechanisms of muscle damage resulting from BFR and critically evaluated the available literature on the application of BFR, do not support the hypothesis that the application of BFR in combination with low-intensity exercises increased the incidence of muscle damage. Instead, current literature suggests that minimal or no muscle damage occurs with this type of exercise. No prolonged decrease in muscle function, prolonged muscle edema, or dissimilar muscle pain classifications to a low load submaximal control and no elevation in blood biomarkers of muscle damage were observed.
The available evidence makes it impossible to conclude in favor of an anti-or proinflammatory response of the BFR technique in the presence of DOMS. As has already been explained, DOMS can occur after exhaustive and/or unusual exercises, particularly in activities involving eccentric muscle contractions that result in pain, inflammation, and edema and it is a complex area of study since there are several factors such as gender, age, nutrition, level of physical conditioning, genetics, and familiarity with the exercise task, which influence the magnitude of the decrease in performance and recovery time after exercise [39]. In addition, a variety of external factors, such as the type of contraction, duration, and intensity of exercise, may also influence the magnitude of the inflammatory response, and the release of muscle proteins into the circulation after muscle damage, caused by exercise [42]. Furthermore, DOMS can be evaluated indirectly using various methods, including blood markers [43], pain scales [44], ROM measurements, or muscle function and strength (Maximum voluntary contraction-MVC) [40]. Possibly the absence of definite conclusions may be due to the aforementioned causes of heterogeneity between the published studies. Nevertheless, the data in the present study seems to indicate that low load exercise (20 to 30% of 1RM) combined with BFR was not a sufficient stimulus to study the benefits of the occlusion technique, and these studies failed to show any difference between the control and experimental groups. On the other hand, high restrictive pressure during eccentric exercise seems to promote greater DOMS and recovery time, while postconditioning BFR seems to have a protective role in DOMS symptoms.
In general, the studies included in this review presented a reduced sample size, consisting mainly of men, with distinctive protocols, both for training and BFR. They had moderate classification in the PEDro scale, and the absence of blindness in the evaluators and participants was frequent. The main limitation of this systematic review was the absence of gray literature, however, the inclusion of google scholar as a database tried to overcome this limitation. Moreover, the choice of keywords could have been another limitation. Nevertheless, the inclusion of numerous synonyms was the strategy to overcome this limitation.

Conclusions
The results from the present study seem to advocate the choice of high restrictive pressures, specifically designed for each participant, combined with eccentric exercise to induce DOMS and greater recovery time. This pro-inflammatory effect could be used to induce greater adaptations in terms of muscle hypertrophy and strength. Conversely, postconditioning application, with predetermined restrictive pressure, could be linked to a more protective effect on DOMS. This post-exercise application of BFR ranged between three and five minutes protocols and one to three times of occlusion.
However, the results from this literature review suggest that the effect of BFR on DOMS is not consensual and is still a controversial topic in the scientific literature since some studies support the pro-inflammatory effects of the technique, while other studies support the anti-inflammatory effect or no effect. These differences may be due to the dissimilarities between exercise and intervention protocols. In this sense, further studies of good methodological basis are still needed, in larger samples, to establish protocols and parameters of exercise and intervention, as well as to confirm the efficacy of BFR on DOMS.

Conflicts of Interest:
The authors declare no conflict of interest.