Title Page (Showing Author Information)

MAIN TITLE: Muscle failure promotes greater muscle hypertrophy in low-load but not in high-load

resistance training

RUNNING HEAD: Muscle failure versus not failure

AUTHORS: Thiago Lasevicius2, Brad J. Schoenfeld4 , Carla Silva-Batista2,3, Talita de Souza Barros1,

André Yui Aihara5, Helderson Brendon1, Ariel Roberth Longo1, Valmor Tricoli2, Bergson de Almeida

Peres1, Emerson Luiz Teixeira1,2*

INSTITUTION AND AFFILIATIONS: 1Paulista University, UNIP, São Paulo, SP – Brazil;

2
School of Physical Education and Sport, University of São Paulo, São Paulo, SP – Brazil; 3School of Arts,

Sciences and Humanities, University of São Paulo, São Paulo, SP – Brazil; 4Department of Health Sciences,

CUNY Lehman College, Bronx, NY – USA; 5America`s Diagnostics S/A, São Paulo, SP – Brazil

CORRESPONDING AUTHOR

Emerson Luiz Teixeira

Address: School of Physical Education and Sport, University of São Paulo, Av. Prof.

Mello Moraes, 65, 05508-030, São Paulo

Email: emerson_teixeira2014@usp.br

Tel: +551121661000

This manuscript is original and not previously published, nor is it being considered

elsewhere until a decision is made as to its acceptability by the JSCR Editorial Review

Board. No funding was received for this study from National Institutes of Health (NIH),

Welcome Trust or Howard Hughes Medical Institute (HHMI). The authors declare they

have no conflict of interest. The results of the present study do not constitute endorsement

by the authors or the National Strength and Conditioning Association (NSCA).

Manuscript ( NO AUTHOR INFORMATION - Manuscript Text
Pages, including References and Figure Legends)

MAIN TITLE
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3 Muscle failure promotes greater muscle hypertrophy in low-load but not in high-load resistance training
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ABSTRACT
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3 The purpose of this study was to investigate the effects of an 8-week resistance training
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6 program at low and high loads performed with and without achieving muscle failure on
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8 muscle strength and hypertrophy. Twenty-five untrained men participated in the 8-week
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study. Each lower limb was allocated to 1 of 4 unilateral knee extension protocols:
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13 repetitions to failure with low load (LL-RF; ~34.4 repetitions); repetitions to failure with
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15 high-load (HL-RF; ~12.4); repetitions not to failure with low load (LL-RNF; ~19.6
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18 repetitions), and; repetitions not to failure with high-load (HL-RNF; ~6.7 repetitions). All
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20 conditions performed 3 sets with total training volume equated between conditions. The
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23 HL-RF and HL-RNF protocols used a load corresponding to 80% 1RM, while LL-RF and
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25 LL-RNF trained at 30% 1RM. Muscle strength (1RM) and quadriceps cross sectional area
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(CSA) were assessed pre- and post-intervention. Results showed that 1RM changes were
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30 significantly higher for HL-RF (33.8%, ES: 1.24) and HL-RNF (33.4%, ES: 1.25) in the
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32 post-test when compared with the LL-RF and LL-RNF protocols (17.7%, ES: 0.82 and
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35 15.8%, ES: 0.89, respectively). Quadriceps CSA increased significantly for HL-RF
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37 (8.1%, ES: 0.57), HL-RNF (7.7%, ES: 0.60) and LL-RF (7.8%, ES: 0.45), whereas no
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40 significant changes were observed in the LL-RNF (2.8%, ES: 0.15). We conclude that
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42 when training with low loads, training with a high level of effort seems to have greater
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45 importance than total training volume in the accretion of muscle mass, whereas for high
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47 load training muscle failure does not promote any additional benefits. Consistent with
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previous research, muscle strength gains are superior when using heavier loads.
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53 Keywords: muscular failure, muscle mass, strength, low load and high load.
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INTRODUCTION
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2 For many years, high-load resistance training (HL-RT) (i.e., ≥ 70% 1RM) has
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5 been recommended as the main strategy to stimulate gains in muscle strength and mass
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7 (17). However, emerging research has challenged this notion from a hypertrophy
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10 standpoint, with numerous studies reporting similar changes in muscle growth between
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12 low-load resistance training (LL-RT) (i.e., <50% 1RM) and HL-RT (16, 18, 22, 24, 33).
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Alternatively, greater strength gains have been consistently observed for HL-RT versus
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17 LL-RT (16, 18, 22, 24, 33).
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20 It also has been proposed that resistance training performed until muscle failure is
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23 necessary to maximize adaptations in muscle strength and hypertrophy (7, 28, 33). This
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25 claim is based on the hypothesis that it is necessary to perform repetitions until muscle
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failure for the complete recruitment of high-threshold motor units, which comprise type
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30 II muscle fibers (30, 39). Since type II muscle fibers have a greater potential to increase
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32 strength (35) and are more susceptible to hypertrophy than type I fibers (12), muscle
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35 failure seemingly would be an important stimulus to maximize muscle adaptations.
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37 However, there is evidence that a high level of muscle activity can be achieved by HL-
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40 RT before reaching muscle failure (34), thereby calling into question the need to train to
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42 failure. Findings from longitudinal studies on the topic are conflicting with some studies
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45 showing advantages for achieving muscle failure (7, 32, 36) while others reporting no
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47 benefit (21, 25, 30). A confounding issue in these studies is that advantages for muscle
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failure with HL-RT occurred concomitantly with a greater total training volume,
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52 suggesting that positive results may have been induced by a higher total training volume
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54 rather than muscle failure. Thus, it is difficult to draw conclusions from the literature as
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57 to the role of muscle failure since studies on the topic performed a similar number of
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59 repetitions in the failure and non-failure groups (19) or did not equalize the total training
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volume (7, 21). It is well established that total training volume plays an important role in
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2 muscular strength and hypertrophy (27, 32) and thus this variable must be matched
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5 between groups to determine causality as to the role of training to failure in promoting
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7 muscular adaptations.
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The present study aimed to investigate the volume-equated effects of HL-RT and
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13 LL-RT performed with and without muscle failure on muscle strength and hypertrophy.
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15 We hypothesized that muscle hypertrophy and strength gains would be similar between
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18 HL-RT protocols with or without muscle failure. Alternatively, we hypothesized that
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20 muscle hypertrophy and strength gains would be greater in the LL-RT protocol performed
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23 to muscle failure when compared with not training to failure.
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29 METHODS
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33 Experimental Approach to the Problem
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36 We employed a longitudinal design to compare the effects of 8 weeks of RT at
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38 low and high loads performed with and without achieving volitional failure on muscle
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41 strength and hypertrophy. Before the start of the training program, participants reported
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43 to the lab and were familiarized with performance of the 1 repetition maximum (1RM)
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46 test performed on a unilateral leg extension machine. After 72 hours, participants repeated
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48 the 1RM test and were considered familiarized with the testing procedures when the inter-
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51 day strength variation was ≤ 5%. The 1RM values for all participants were obtained
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53 within 3 visits. At least 72 hours after the last 1RM test, muscle cross-sectional area
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(CSA) of the quadriceps was obtained via magnetic resonance imaging (MRI). After the
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58 MRI, each participant’s limb was allocated in a randomized fashion to one of the two
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60 training protocols based on 1RM and CSA values: HL-RT leading to repetition failure
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(HL-RF, 13 limbs); LL-RT leading to repetition failure (LL-RF, 12 limbs). The

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2 contralateral leg was allocated to the same loading protocol of the opposing leg but
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5 without achieving failure: HL-RT not leading to repetition failure (HL-RNF, 13 legs);
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7 and LL-RT not leading to repetition failure (LL-RNF, 12 limbs). HL-RNF and LL-RNF
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10 protocols performed the same total training volume as HL-RF and LL-RF, respectively.
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12 Training was carried out twice per week on non-consecutive days for 8 weeks. After 4
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weeks of training, 1RM was retested 72 hours after the eighth training session to readjust
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17 training load in the ensuing weeks (5-8 weeks). Quadriceps CSA was assessed 72 hours
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19 after completing the last training session, with subsequent assessment of 1RM 48 hours
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22 later. The subjects’ rating of perceived exertion (RPE) was assessed at the end of each
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24 training bout. Subjects were instructed to maintain their usual and customary dietary
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27 practices throughout the course of the study.
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Participants
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36 Thirty-two male individuals volunteered to participate in this study. Participants
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38 were physically active but none had engaged in any kind of regular resistance training or
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41 regular participation in any strength-based sporting activity for the lower limbs in the past
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43 6 months prior to study, nor did they participate in any parallel program of physical
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training during the study period. All participants were free from cardiovascular and/or
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48 neuromuscular disorders. Seven participants withdrew from the study due to personal
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50 reasons; therefore, data from twenty-five participants were considered for analysis. Group
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53 characteristics are shown in Table 1. Participants were informed about the benefits,
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55 discomforts and possible risks of the study and signed a free and informed consent term
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58 before participation. The study was conducted according to the Declaration of Helsinki,
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60 and the University’s Research Ethics Committee approved the experimental protocol.
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3 - PLEASE INSERT TABLE 1 HERE –
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9 Maximum dynamic strength test
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12 Unilateral 1RM knee extension testing of the right and left lower limbs was
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15 performed as per American Society of Exercise Physiologists recommendations (2). The
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17 test was performed in a leg extension machine (10A-CO12 CAP, Gervasport, Cotia, SP,
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20 Brazil) under isotonic conditions. Participants started with a 5-minute warm-up running
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22 on a treadmill at 9km.h-1, followed by 3 minutes of light stretching of the lower limbs.
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24 They then performed a specific warm-up comprised of 2 sets: in the first set they
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27 performed 8 repetitions at approximately 50% 1RM; in the second set they performed 3
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29 repetitions at approximately 70% 1RM. A 2-minute rest interval was used between warm-
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32 up sets. Both loads were estimated based on the participant’s familiarization sessions.
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34 Three minutes after the specific warm-up, subjects tested for their 1RM, herein defined
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37 as performance of a complete cycle of the exercise with the greatest load they could lift.
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39 A complete cycle involved performing a full knee extension (0º) starting from the initial
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position of 90° of flexion and then returning to the starting position while maintaining
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44 control throughout the entire movement range. The load was progressively increased
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46 from the last set of the specific warm-up until the participant could not perform the
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49 exercise in the required manner. A 3-minute rest interval was used between attempts. The
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51 greatest load lifted during the trials was considered as 1RM. Final values were obtained
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54 in a maximum of 5 attempts. The coefficient of variation (CV) between two measures
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56 performed 72 hours apart was 3.3%.
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Quadriceps Cross-Sectional Area

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3 Quadriceps CSA was obtained through MRI (Signa LX 9.1; GE Healthcare,
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6 Milwaukee, WI, USA). Participants assumed a supine position in the MRI unit with knees
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8 extended and lower limbs straight. Subjects remained lying quietly for 20 minutes prior
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to image acquisition. A bandage was used to restrain limb movements during the test. An
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13 initial reference image was obtained to determine the perpendicular distance from the
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15 greater trochanter of the femur to the inferior border of the lateral epicondyle of the femur,
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18 which was defined as the segment length. Quadriceps CSA was measured at 50% of the
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20 segment length with 0.8-cm slices for 3-seconds. The pulse sequence was performed with
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23 a field of view between 400 and 420 mm, time of repetition of 350 ms, eco time from 9
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25 to 11 ms, two signal acquisitions, and a matrix of reconstruction of 256 x 256 mm. The
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images were then transferred to a workstation (Advantage Workstation 4.3; GE
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30 Healthcare) to determine quadriceps CSA. The quadriceps CSA images were traced in
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32 triplicate by a trained researcher, and their mean values were used for further analysis.
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35 The segment slice was divided into skeletal muscle, subcutaneous fat tissue, bone, and
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37 residual tissue. Quadriceps CSA was determined by subtracting the bone and
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40 subcutaneous fat area. The CV between two measures performed 72 hours apart was
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42 0.87%.
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49 Resistance Training Protocols
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52 Participants performed the unilateral knee extension exercise using a conventional
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55 leg-extension machine (10A-CO12 CAP, Gervasport, Cotia, SP, Brazil), with training
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57 carried out twice a week for 8 weeks (total of 16 sessions). At the beginning of each
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59 training session participants performed a general warm-up at 9 km h-1 on a treadmill for
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5 minutes, followed by a specific warm-up comprised of 1 set of 5 repetitions at 50%

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2 1RM. The general as well the specific warm-up were well tolerated by all subjects and
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5 no one reported tiredness before starting the experimental protocol. One minute
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7 afterward, subjects performed 3 sets of their respective training protocols (i.e. HL-RF and
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10 LL-RF) on one limb until concentric failure. The mean of total number of repetitions in
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12 all sets from HL-RF and LL-RF was then calculated and 60% of these values were used
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to perform each set of HL-RNF and LL-RNF protocols, respectively, on the opposite
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17 limb. Additional sets were performed in the RNF conditions to equate total training
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19 volume between limbs. Thus, the HL-RNF and LL-RNF protocols performed fewer
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22 repetitions per set but with a greater number of sets to achieve the same total training
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24 volume for HL-RF and LL-RF, respectively. The HL-RF and HL-RNF protocols used a
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27 load corresponding to 80% 1RM, while LL-RF and LL-RNF protocols trained at 30%
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29 1RM. A 2-minute rest interval was used between sets. For the muscular failure protocols,
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repetitions were performed until subjects were unable to perform a repetition with a full
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34 range of motion using proper form (i.e., starting from 90º of flexion to full knee extension
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36 at 0º).
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43 Number of sets, repetitions and Total Training Volume
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46 We calculated the average number of sets and number of repetitions performed
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49 per set throughout training period (16 training sessions). The total training volume was
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51 calculated as the sum of the training volume (number of sets x number of repetitions x
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54 external load) performed throughout training period.
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60 Perceptual response
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Thirty minutes after the end of each experimental condition (i.e. RF and RNF),
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2 subjects reported RPE using the CR10 scale (1). All participants were given standardized
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5 instructions as to perceptual response of exertion according to the recommendations of
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7 Borg (1). Participants were asked to give a number corresponding to their perceived
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10 intensity of effort, strain and/or fatigue experienced during the exercise session. A value
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12 of “0” represented “absolutely nothing” from an exertion standpoint and “10” represented
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a “maximal exertion”.
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31 Statistical analysis
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34 Data are presented as means and standard deviations. Data normality was tested
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36 by the Shapiro-Wilk test and the visual inspection of box-plot to observe the presence of
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39 outliers. After confirming data normality, a mixed model for repeated measures was
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41 applied with two factors: experimental protocols (HL-RF, HL-RNF, LL-RF and LL-
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44 RNF) and time (pre and post) for the quadriceps CSA. To rule out confounding of lower
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46 limb dominance on strength gains, we employed an ANCOVA with dominant and non-
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49 dominant limbs as covariates. For RPE, a mixed model for repeated measure was applied,
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51 assuming experimental protocols (HL-RF, HL-RNF, LL-RF and LL-RNF) and times (1-
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16 sessions) as fixed factors, and participants as a random factor. Four different structures
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56 of covariance matrices were tested and the Bayesian information criterion (lowest BIC)
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58 was used to select the model that best fit each individual data set. The total number of
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sets, repetitions and total training volume were compared by a one-way analysis of
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2 variance (ANOVA). In all analyses, the Tukey post hoc was used for multiple
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5 comparisons when a significant F value was found. The effect size (ES) was calculated
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7 as the post-training mean minus the pre-training mean divided by the pooled pre-training
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10 standard deviation (23), where the following categories were used to evaluate the
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12 magnitude of the change for 1RM and quadriceps CSA: ≤0.49 small; 0.50-0.79 medium
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and ≥0.80 large (5). The significance level was set a priori at p ≤ 0.05. Data were analyzed
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17 using the SAS 9.3 statistical package.
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30 RESULTS
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Quadriceps Cross-Sectional Area (CSA)
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37 There was a significant time x condition interaction in quadriceps CSA (p=0.002).
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Quadriceps CSA increase significantly pre- to post-test in HL-RF (85.0 ± 12.1 to 91.7 ±
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42 11.4 cm2, ES: 0.57, p = 0.001), HL-RNF (85.1 ± 10.9 to 91.5 ± 10.4, ES: 0.60, p = 0.001)
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44 and LL-RF (85.7 ± 14.3 to 92.3 ± 14.8 cm2, ES: 0.45, p = 0.001), with no significant
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47 differences between these protocols (HL-RF vs. HL-RNF, Confidence interval (CI) = -
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49 2.25 to 1.80, p = 0.81; HL-RF vs. LL-RF, CI = -2.25 to 1.80, p = 081; HL-RNF vs. LL-
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52 RF, CI = -0.51 to 1.38, p = 0.331). However, no significant increase in quadriceps CSA
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54 was noted from pre- to post-test for LL-RNF (85.8 ± 14.7 to 88.0 ± 14.6 cm2, ES: 0.15,
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CI = -1.9561 to 3.533, p = 0.994) (Fig. 1A). Additionally, quadriceps CSA increases at
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59 post-test in HL-RF, HL-RNF and LL-RF were significantly higher when compared to
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LL-RNF (CI = 2.094 to 9.152, p= 0.004; CI = 2.172 to 6.039, p= 0.001; CI = 2.802 to

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2 7.905, p = 0.001, respectively).
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9 Maximum dynamic strength test (1RM)
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12 There was significant time x condition interaction in unilateral leg extension 1RM
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15 (p= 0.0001). The 1RM values increased pre- to post-test in all training protocols (p<
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17 0.0001). However, values for HL-RF (75.5 ± 19.2 to 99.3 ± 19.0 kg, ES: 1.24) and HL-
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20 RNF (75.1 ± 18.4 to 99.4 ± 20.4 kg, ES: 1.25) were significantly greater when compared
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22 with the LL-RF and LL-RNF protocols (76.1 ± 14.9 to 89.2 ± 16.9 kg, ES: 0.82, CI =
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24 8.728 to 24.73, p = 0.001 and 75.0 ± 11.8 to 86.5 ± 13.7 kg, ES: 0.89, CI = 9.273 to
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27 28.45, p = 0.001, respectively). No significant differences in pre- to post-test 1RM values
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29 were detected between protocols of the same intensity (HL-RF vs. HL-RNF, CI = -4.79
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32 to 4.96, p = 0.972 and LL-RF vs. LL-RNF, CI = -9.20 to 3.87, p = 0.383) (Fig. 1B).
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43 Number of sets, repetitions and total training volume
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50 The average number of sets and repetitions performed by HL-RF, HL-RNF, LL-
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52 RF and LL-RNF were 3.0 ± 0 sets and 12.4 ± 3.1 reps, 5.5 ± 0.5 sets and 6.7 ± 1.6 reps,
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55 3.0 ± 0 sets and 34.4 ± 7.7 reps and 5.4 ± 0.6 sets and 19.6 ± 4.1 reps, respectively. Total
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57 training volume values were similar between HL-RF, HL-RNF, LL-RF and LL-RNF
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(34853 ± 8020 kg, 34803 ± 7857 kg, 34576 ± 16372 kg and 34592 ± 16326 kg, p > 0.05,
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2 respectively).
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12 RPE
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16 There was a significant time x condition interaction for RPE (p < 0.05). The RPE
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18 was significantly greater in all training sessions for protocols performed until muscle
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failure (HL-RF and LL-RF) compared with protocols without muscle failure (HL-RNF
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23 and LL-RNF) (p < 0.05) (Fig. 2).
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- PLEASE INSERT FIGURE 2 HERE –
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48 DISCUSSION
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51
52
The present study investigated the effects of volume-equated low- and high-load
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54 resistance training with and without muscle failure on muscle strength and hypertrophy
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56 in untrained, physically active men. Our main findings were: 1) When performing low-
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59 load resistance training, training with a very high level of effort is necessary to increase
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muscle hypertrophy; 2) muscle failure with high-load resistance training confers no

1
2 additional benefits on muscle strength and hypertrophy; 3) RPE is greater when training
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5 to failure as opposed to stopping short of failure, independent of load.
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8 It has been suggested that low-load resistance training only promotes similar
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muscle hypertrophy to high load resistance training when the low load condition is
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13 performed to muscle failure (10, 22, 24, 26). Support for this hypothesis is based on acute
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15 findings showing that low-load resistance training promoted a greater increase in
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18 myofibrillar protein synthesis only when carried out until muscle failure and with a high
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20 volume of training (3, 4). Moreover, low-load training with blood flow restriction (BFR)
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23 to failure has been shown to produce superior hypertrophy compared to a repetition-
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25 matched control performing the same exercise without BFR (20); alternatively, when
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low-load training without BFR is taken to failure, hypertrophy is similar to the BFR
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30 condition (9). Our findings provide longitudinal confirmation for this hypothesis with
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32 direct measures of long-term hypertrophy in untrained men. These results were seen
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35 regardless of training volume given that only LL-RF increased muscle CSA despite total
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37 training volume being equated between conditions. Taken as a whole, these findings
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40 indicate that when engaging in low-load resistance training, performing sets with a high
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42 level of effort is more important than a higher training volume when the objective is to
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45 increase muscle hypertrophy.
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48 Training to failure may heighten metabolic stress due to prolonged energy use
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50 from the glycolytic system and the associated buildup of metabolites could enhance the
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52
53 anabolic milieu, potentially leading to greater muscle hypertrophy (13, 19, 28). Consistent
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55 with the size principle, higher threshold motor units are recruited early during a set of
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58 heavy load training whereas the initial repetitions in a low-load set primarily involve
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60 recruitment of lower threshold motor units; only when a low-load set continues to the
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point where greater levels of force are needed to sustain contractions do higher threshold
1
2 motor units become activated. Accordingly, it has been hypothesized that the fatigue
3
4
5 associated with training to muscle failure results in the progressive recruitment of a
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7 greater number of high-threshold motor units, which conceivably could enhance muscle
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9
10 hypertrophy (29, 38). However, when performing repetitions in proximity to failure, but
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12 not going to failure, muscle activity seems to be the same as when repetitions are taken
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15
to failure (25, 34). To date, only one study has investigated the effect of muscle failure in
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17 low- and high-load resistance training. Nóbrega et al. (23) randomized untrained men to
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19 perform resistance training using either muscle failure or volitional interruption at low-
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22 and high-loads (e.g. 30% and 80% 1RM, respectively). After 12 weeks, similar increases
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24 in muscle thickness were observed both with and without muscle failure independent of
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27 the load used. Our results conflict with those of Nóbrega et al. (23), given that we showed
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29 significantly greater muscle growth when low-load training was performed to failure
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31
32
versus not to failure. A possible explanation for these discrepancies is that in the study by
33
34 Nóbrega et al. (23) the subjects in the volitional interruption condition terminated a set
35
36 when they felt sufficiently fatigued. This approach resulted in performance of a
37
38
39 comparable number of repetitions between conditions, indicating the volitional
40
41 interruption group was in close proximity to failure. Alternatively, our study showed
42
43
44 substantial differences in the number of repetitions performed between the low-load
45
46 failure and non-failure conditions (34.4 versus 19.6 repetitions, respectively). Combined,
47
48
49 the literature suggests that a high level of effort is required to elicit hypertrophy during
50
51 low-load training, and simply increasing volume will not augment results if the effort
52
53
54
expended is low.
55
56
57 As opposed to our findings regarding low-load resistance training, muscle failure did not
58
59 provide additional benefits on muscular adaptations when training at high resistance
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training loads in untrained men. This result is largely in agreement with the prevailing
1
2 body of literature on the topic. Sampson and Groeller (31) found similar increases in
3
4
5 elbow flexors CSA after 12 weeks of regimented HL-RT (85% 1RM) performed either
6
7 until failure or not to failure. Martorelli et al. (21) also showed similar increases in elbow
8
9
10 flexors CSA after 10 weeks of HL-RT between the failure group and the non-failure
11
12 group, indicating no advantage in performing sets to muscle failure. Taken as a whole, it
13
14
15
can be inferred that muscle fibers are sufficiently stimulated to hypertrophy when high-
16
17 load resistance training sets are stopped short of concentric failure and that further
18
19 repetitions do not elicit additional benefits (25, 34).
20
21
22
23 Regarding muscle strength, we found that muscle failure is not obligatory to
24
25 maximize muscle strength, independent of training load in untrained men. While all
26
27
28
groups increased muscle strength, HL-RF (33.8%) and HL-RNF (33.4%) elicited greater
29
30 increases when compared to the LL-RF and LL-RNF protocols (17.7 % and 15.8%,
31
32 respectively). Our data are consistent with previous studies showing that heavier loads
33
34
35 are required to maximize gains in dynamic strength (18, 22, 26, 33). Of the studies that
36
37 have investigated the effect of muscle failure in high-load resistance training on muscle
38
39
40 strength, our results are in agreement with those of Folland et al. (11), who compared
41
42 high and low fatigue protocols and found no difference between groups after nine weeks
43
44
45 of training. Similarly, Izquierdo et al. (15) reported no additional strength benefits from
46
47 training to failure in lower and upper body exercise. In an attempt to provide clarity on
48
49
50
the body of literature, Davies et al. (6) carried out a meta-analysis that found similar
51
52 strength increases when high load resistance training was performed to failure versus not
53
54 to failure.
55
56
57
58 Only one study has endeavored to investigate the effect of muscle failure on
59
60 muscle strength in low-load resistance training. Nóbrega et al. (25) found that muscle
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failure did not increase muscle strength over and above that achieved by the volitional
1
2 interruption group. However, as previously mentioned, the number of repetitions
3
4
5 completed in the volitional interruption group was similar to the muscle failure group,
6
7 obscuring the ability to draw inferences about the importance of muscle failure on low-
8
9
10 load strength gains. When taken in conjunction with our findings, it can be inferred that
11
12 muscle failure is not a significant factor for increasing muscle strength in low-load
13
14
15
resistance training. Given the design of our study, the evidence suggests that achieving a
16
17 certain amount of volume of training may be more important to maximize muscle strength
18
19 than performing repetitions until muscle failure.
20
21
22
23 The RPE was significantly greater in all training sessions for protocols performed
24
25 until muscle failure. This suggests that training to muscle failure in beginners may not
26
27
28
only induce unnecessary exertion, but also may impair muscle recovery due to the higher
29
30 metabolic and neuromuscular impact. In addition, training with a high level of
31
32 unnecessary effort could reduce exercise enjoyment, ultimately resulting in a lower
33
34
35 adherence to the resistance training program (36).
36
37
38 The present study is not without limitations. First, while subjects were instructed
39
40
41 to maintain their usual and customary diet, we did not attempt to monitor nutritional
42
43 intake, which may have influenced results between conditions. However, the within-
44
45
46
subject design as well as the randomization process would have helped to minimize any
47
48 potential variations attributed to this variable. Second, the findings are specific to
49
50 untrained young men; it is not clear whether training to failure may be necessary to
51
52
53 promote a growth response in women, the elderly, or those who are resistance trained.
54
55 Third, findings are specific to performance of a single-joint lower body exercise, and thus
56
57
58 cannot necessarily be generalized to upper body and multi-joint exercises. Fourth, we
59
60 cannot rule out the possibility that a cross-education effect may have influenced our
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 18

results since muscle failure condition always was performed first. However, our results
1
2 are in accordance with other studies (21, 31) showing that performing repetitions to
3
4
5 failure is not the major issue to development of muscle strength; thus, if the cross-
6
7 education did in fact occur, it was not sufficient to confound results. Fourth, our training
8
9
10 protocol used only the leg extension exercise, limiting generalizability to hypertrophic
11
12 changes associated with failure training using other exercises and in regions of the body
13
14
15
other than the quadriceps. Finally, although we used a gold-standard assessment for
16
17 hypertrophy (MRI), measurements of CSA were taken at the mid-point of the thigh.
18
19 Research shows that the quadriceps femoris often hypertrophies in a non-uniform manner
20
21
22 along the length of the muscle with persistent resistance training (8, 37). It is possible that
23
24 training to failure may induce regional specific hypertrophy in the proximal or distal
25
26
27 region that would not have been accounted for in our testing protocol, although it is
28
29 difficult to envision a rationale as to why such an effect would occur.
30
31
32
33
34
35
36 PRATICAL APPLICATIONS
37
38
39 Based on our findings, we propose that a high level of effort is required to elicit
40
41
42
hypertrophic adaptations in low-load resistance training in beginners, even with total
43
44 training volume matched. Alternatively, muscle strength increases in total training
45
46 volume-equated low load are similar independent whether training is carried out to failure
47
48
49 in untrained men. When performing resistance training at high loads, muscle failure does
50
51 not confer any additional strength or hypertrophy-related benefits compared to stopping
52
53
54 well short of failure provided total training volume is equated between conditions in
55
56 novice trainees.
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CONFLICT OF INTEREST
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3 The authors declare that they have no conflict of interest.
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39. Willardson JM. The application of training to failure in periodized multiple-set
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52 Table Legend.
53
54 TABLE 1 - HL-RF= High-load resistance training leading to repetition failure, HL-RNF=
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56
high-load resistance training not leading to repetition failure; LL-RF= low-load resistance
57 training leading to repetition failure, LL-RNF= low-load resistance training not leading
58 to repetition failure.
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1
2 Figure Legend.
3
4
5
6 FIGURE 1 - A: Quadriceps cross-sectional area (CSA); and B: Maximum dynamic
7 strength (1RM) (mean ± SD) evaluated before (pre) and after 8 weeks (post). High-load
8 resistance training leading to repetition failure (HL-RF); high-load resistance training not
9 leading to repetition failure (HL-RNF); low-load resistance training leading to repetition
10
11 failure (LL-RF); and low-load resistance training not leading to repetition failure (LL-
12 RNF). *Significantly different compared with pre (p<0.002); #Significantly different
13 when compared with LL-RF and LL-RNF (p<0.002).
14
15
16
17 FIGURE 2 - Ratings of perceived exertion (RPE) (mean ± SD) evaluated in each training
18 session. High-load resistance training leading to repetition failure (HL-RF); high-load
19 resistance training not leading to repetition failure (HL-RNF); low-load resistance
20 training leading to repetition failure (LL-RF); and low-load resistance training not leading
21
22 to repetition failure (LL-RNF). *Significantly different compared with pre (p<0.002);
#
23 Significantly different when compared with HL-RNF and LL-RNF (p<0.05).
24
25
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27
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29
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37
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Table

Baseline Values HL-RF (n = 13) HL-RNF (n = 13) LL-RF (n = LL-RNF (n = 12)

12)
Age (years) 23.8 ± 4.9 23.8 ± 4.9 24.3 ± 4.8 24.3 ± 4.8
Heigh (cm) 176.6 ± 7.2 176.6 ± 7.2 175.4 ± 6.0 175.4 ± 6.0
Body Mass (kg) 74.8 ± 12.5 74.8 ± 12.5 73.7 ± 13.3 73.7 ± 13.3
1RM (kg) 75.5 ± 19.2 75.1 ± 18.4 76.1 ± 14.9 75.0 ± 11.8
TABLE 1. Participant characteristics by group.
Figure 1 Click here to access/download;Figure;Figure 1.tiff
Figure 2 Click here to access/download;Figure;Figure 2 .tiff