In The BFR Pros workshop, we discuss how metabolite-induced fatigue and cellular swelling are most likely the primary mechanisms associated with why we see hypertrophy in low-load BFR exercise. However, there are other proposed mechanisms that have been mentioned in the literature that researchers have ascribed to BFR training itself. These other proposed mechanisms – increased hormone release (growth hormone, GH; Insulin-like growth factor-1, IGF-1), systemic/cross-transfer effects and satellite cell proliferation- can largely be explained by methodological limitations of the studies. Namely, these mechanisms can be explained if accounting for proximity to failure, the influence of ischemia during muscle contractions and/or the exercise type (aerobic vs. resistance training). The purpose of this short paper is to highlight these three proposed mechanisms and provide evidence-based rationales as to why the benefits observed with BFR are not likely directly related to these factors.
Most BFR studies are performed work matched, such that the BFR group performs an equal amount of work as the free-flow condition (ie 30-15-15-15 or BFR exercises to failure, free-flow matches repetitions). However, in those studies where BFR and the free-flow condition are performed to volitional failure, similar levels of hormone release (GH and IGF-1) were observed between conditions (1-2). In one study that showed higher levels of acute GH release in BFR compared to free-flow condition, there was no relationship observed with metabolic accumulation (lactate), suggesting that local factors (ie stimulation of III-IV afferents due to the restriction) may have increased GH expression as a response to stress (3). Pierce and colleagues’ (2006) (4) study supports this assertion as GH was not increased in a passive swelling protocol but was significantly elevated when combined with exercise and those that experienced the greatest fatigue (drop in maximum voluntary contraction, MVC) also had the highest levels of GH release. While more research is needed to elucidate the relationship between hormonal responses, BFR training and hypertrophy, other studies in free- flow resistance training have failed to link acute- or chronic levels of GH release to hypertrophy (Morton, 2018; Fink, 2018).
Systemic effects, or cross-transfer effects, are frequently discussed with respect to hormone release and BFR training as a mechanism of action for BFR. Cross-transfer effects involve positive adaptations (whether strength or muscle hypertrophy) in tissues remote to the application of BFR (7-9). The idea is that local hormones produced through BFR exercise travel throughout the body via the bloodstream and can act as effectors for eliciting hypertrophy and strength on muscle tissue as long as it is somewhat sensitized by a low-load effort (ie 3×10 repetitions of bicep curls at 50% 1RM) (7-8). The cornerstone study supporting the systemic effects of BFR was performed by Madarame and colleagues (2008). They took 15 untrained men and randomized them into BFR or non-BFR groups and each exercised twice a week for 10 weeks. Each participant did elbow flexion exercise on one arm for 3 sets of 10 repetitions at 50% 1RM followed by knee flexion and extension exercises in a 30-15-15 repetition scheme at 30% 1RM (7). The untrained arm served as the control arm condition while the BFR group performed all leg exercises with BFR (7). After 10 weeks, the individuals who performed BFR leg exercise demonstrated larger percent changes in the trained arm elbow flexor CSA and isometric strength compared to the no-BFR group, supporting the notion of a systemic effect of BFR training (7). In support of their hypothesis, elevated levels of norepinephrine and a trend towards higher levels of GH were observed in the BFR group compared to the no-BFR group (7). However, other studies have failed to replicate the results of Madarame (2008), instead showing only increases in remote elbow flexor strength in the trained group with no increases in muscle CSA (8) or no increases at all in proximal muscle groups (9). Moreover, a recent study in individuals with low back pain performing 10 weeks of BFR exercise twice per week on the legs and calves prior trunk extensor exercise at 25% MVC showed no cross-transfer effect to the erector spinae musculature following training (9). These conflicting results can be explained by relating the exercise bouts to proximity to failure. All of these studies performed non-failure leg protocols and compared them to matched free-flow controls, so it is unknown how close each of the groups were to volitional failure (7-9). Exercising to failure may negate any potential
acute responses (hormone release, neuromuscular activation differences) to the restrictive stimulus by ensuring equal effort by each participant. As such, more research is needed to support this BFR effect as a potential mechanism for its efficacy observed in practice.
Satellite cells (SCs) are thought to be required for hypertrophy as they have been linked to long-term changes in resistance-training induced increases in muscle size (10). The molecular underpinnings of how SCs get recruited to assist in muscle building is beyond the scope of this paper, but in short – a damaging bout of exercise activates a quiescent SC from the basal lamina of the muscle fiber to proliferate, differentiate and then fuse into the muscle fiber to help with repair and growth processes (10). These SCs can either remain in the muscle fiber to help with the creation of new myonuclei to increase growth potential of the muscle fiber or
return back to the basal lamina (10). Indeed, a high frequency BFR training program to failure has shown to increase SC proliferation over low-load free-flow exercise (11), but the exercise comparison free-flow group was work matched. Thus, it is unknown whether proximity to failure was the reason for the observed results or if it was the restrictive stimulus. Other studies showed no changes in SC/myonuclei concentrations after 6- or 12-weeks of BFR training to failure (at 30% 1RM) compared with non-failure high-intensity training (70%+ 1RM) (12-13) or no significant differences in increases between non-failure high-intensity training (10×8 reps at
70%1 RM) and very light non-failure training (10×36 reps at 15.5% 1RM) (14) despite changes in muscle size and strength. These studies highlight that SC proliferation isn’t always predictable in long-term hypertrophy produced by various repetition and loading schemes – with or without
BFR. Last, SCs have been shown to be elevated in response to other types of exercise such as endurance training (15) suggesting that the recruitment of SCs may be linked to a stress response that’s not unique to BFR training.
In summary, the mechanisms that most probably play the largest role in the beneficial adaptations seen in BFR resistance training are related to accelerating the time to volitional failure of the muscles distal to the cuff. Metabolite accumulation and cell swelling secondary to the restrictive cuff provide a window to replicate a similar local muscular environment as
heavier lifting protocols through the earlier recruitment of type 2 fibers at lighter (20-50% 1RM) loads. The other mechanisms – hormone production, cross-transfer effects and SC proliferation are likely secondary reactions to local metabolic stress or BFR application and play variable roles in the response to chronic BFR training (Takada, 2012).
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