This guest post is written by Dr. Anthony Ponce, PT, DPT, MSEd, CSCS, and gives an evidenced-based recommendation for exercise prescription to increase skeletal muscle hypertrophy. For more from Dr. Ponce, follow him on instagram @poncephysiocoach.

Introduction
Skeletal muscle is comprised of different fiber types, which enables it to fulfill a variety of functional demands including being able to alter its profile in response to stimuli. Resistance training has been commonly utilized as a method for increasing strength and size of skeletal muscle. Resistance training can vary in its intensity, the number of sets, the choice of exercise, the order of exercise, and the recovery time between sets. This review will primarily focus on intensity of load. Intensity of load directly impacts the amount of repetitions performed. Intensities over 65% of 1 repetition maximum (RM) have been associated with a higher effectiveness in increasing muscular size. Typically, a high intensity of load would correlate with a low repetition set, and a low intensity of load would correlate with a high repetition set. Low repetitions are utilized primarily for Olympic lifting and powerlifting protocols. These protocols consist of higher intensity levels and may stimulate hypertrophy of fast twitch fibers with little impact on slow twitch fibers. Low repetitions are usually considered repetitions fewer than 5-RM. However, repetition ranges may vary depending on the definition used by the researchers. Lower repetitions target both a higher mechanical tension of the muscle as well as a neurological component of muscle recruitment that aims to increase overall power and strength. A review by Schoenfeld, 2010, correlates mechanical tension as one of the essential mechanisms for skeletal muscle growth. Higher repetitions are utilized in bodybuilding style protocols where the intensity is generally lower while the volume is higher. Higher repetitions for this review will be considered repetitions ranging from 8-12-RM, but they may vary depending on the definition used by the researcher. Bodybuilding style protocols not only promote hypertrophy of the fast twitch fibers but may also promote hypertrophy of the slow twitch fibers. Higher repetition protocols place a higher metabolic stress on the muscle, thereby increasing metabolites, which could provide a relevant additive anabolic stimulus when compared to the higher mechanical tension and stress achieved with heavier loads. The purpose of this review is to examine the current evidence in order to compare the effects of low repetitions vs. high repetitions and their respective impacts on skeletal muscle hypertrophy.

Literature Review
A study by Masuda et al., 1999, examined the effects of resistance training on myoglobin in human skeletal muscle. The researchers utilized two different protocols — a bodybuilding protocol and a powerlifting protocol — and examined whether these protocols differed in their influence of myoglobin adaptation. Eleven untrained subjects were analyzed — 6 for the bodybuilding protocol and 5 for the powerlifting protocol. The mean age, height, and body mass for the bodybuilding group were 28.5 (SD 4.0) years, 173.5 (SD 1.6) cm and 70.7 (SD 5.0) kg, respectively, and 27.6 (SD 3.7) years, 173.6 (SD 6.1) cm and 69.8 (SD 5.1) kg, respectively for the powerlifting group. There was no significant differences in these factors between groups. The exercise protocol consisted of concentric knee extensions carried out until subjects were too fatigued to continue and performed twice per week for 8 weeks. The bodybuilding protocol consisted of 40-80% of 1-RM over the course of nine trials with a 30-second rest between sets. The powerlifting protocol consisted of 90% of 1-RM over the course of five trials with a 3-minute rest. To measure the effects of the protocols, the researchers performed muscle biopsies on the right vastus lateralis skeletal muscle before and after the 8-week period. The researchers found no significant difference in the fiber composition between protocols. They also found an increase in muscle fiber cross-sectional area in all protocols in response to the 8-week training with no significant differences between protocols.  

A different study compared two training protocols and their effects on strength, cross sectional area, specific tension, and anthropometric changes (Chestnut and Docherty., 1999). Twenty-four untrained men were analyzed, aged 24.2 ± 1.76 years and weighing 80.4 ± 13.9 kg. The training protocols consisted of 6 sets of 4 repetitions (85% of 1-RM) carried out until failure for the powerlifting group and 3 sets of 10 repetitions (70% of 1-RM) carried out until failure for the bodybuilding group. Both groups utilized upper-body resistance training exercises. The training was performed 3 times per week for 10 weeks with at least 48 hours between sessions. Volume was equated for both protocols. Magnetic resonance imaging was carried out to determine the muscle cross sectional area of the right arm during weeks 0 and 10. Muscle cross sectional area was calculated through the combination of the forearm flexors and extensors. The researchers found a significant increase in the midpoint and the distal cross sectional area for the both groups. There was no significant difference on the magnitude of the cross sectional values between groups. The researchers concluded that 4-RM and 10-RM weight training protocols equated for volume produced a similar muscular adaptation after short-term training in untrained subjects. 

Another study compared the effects of three different resistance-training protocols on the vastus lateralis muscle (Campos et al., 2002). Thirty-two healthy untrained men volunteered for this study — age 22.5 ± 5.8 years, height 178.3 ± 7.2 cm, and body mass 77.8 ± 11.9 kg. Twenty-seven subjects were randomly assigned to the three training groups and 5 subjects served as the control. The resistance training protocols consisted of a low repetition group that performed 3-5-RM for four sets with a 3-minute rest between sets and exercises, an intermediate repetition group that performed 9-11-RM for three sets with a 2-minute rest between sets and exercises and a high repetition group that performed 20-28-RM for two sets with a 1-minute rest between sets and exercises. The exercises performed by all groups were lower-body resistance training exercises. The training program lasted 8 weeks and workouts were performed 2 days per week for the first 4 weeks and 3 days per week for the final 4 weeks. Volume was equated for all three resistance-training protocols. Muscle biopsy samples were taken from the vastus lateralis muscle pre and post training. The researchers found a hypertrophic effect only in the intermediate repetition and low repetition groups, with both groups showing a significantly larger cross sectional area after training. No significant changes were found for either the high repetition or control groups. As a result, the researchers concluded that both low and intermediate RM training induce a similar muscular adaptation after short-term training in untrained subjects. 

A study by Kraemer et al., 2004, compared the changes in whole muscle hypertrophy, strength, and power with different resistance training programs. Eighty-five untrained women, age 23.1 ± 3.5 years, were randomized across 5 groups. The groups consisted of two total body training groups, two upper body training groups, and a control group. The total body and upper body training groups were split into a 3-8-RM training range and an 8-12-RM training range. These two resistance ranges were classically periodized over two 3-month periods of time (mesocycle). Each mesocycle started with the higher repetition range and ended with lower 8-RM or 3-RM as prescribed. Participants were measured for cross-sectional area via MRI technology, with assessments performed at weeks 0, 12 and 24 on the mid thigh and upper arm of the dominant limbs. The results found that arm cross-sectional area increased significantly in all training groups on weeks 12 and 24. For thigh cross-sectional area, only the total body training groups exhibited a significant increase in cross-sectional area during all three assessments, and no differences were observed in the control group during any assessment for thigh or arm cross-sectional area. The researchers concluded that a 6-month periodized resistance training program was effective at increasing muscular hypertrophy in all loading ranges in previously untrained women. 

Another study aimed to measure the amount of phospho-Akt and several of its downstream anabolic targets and catabolic targets in human skeletal muscle (Léger et al., 2006). Twenty-five untrained healthy male subjects participated in the study with a mean age of 36 ± 4.9 years. The resistance training protocol lasted 8 weeks. Subjects were split into either low (3-5-RM) or high (20-28-RM) repetition groups with all repetitions to be completed until fatigue. Both resistance programs were designed to be equal in volume. The exercise program consisted of leg press, squat, and leg extension, performed in a fixed order. Subjects were measured by computed tomography to determine the cross sectional area of the quadriceps. The researchers found approximately a 10% increase in quadriceps size after training when compared to the pretraining levels in both groups. They observed a significant muscle hypertrophy following both the low repetition protocol and the high repetition protocol.

A study by Ogasawara et al., 2013, examined low-load resistance exercises to volitional fatigue and their effects on muscle hypertrophy to determine how this response compared to high load resistance training. Nine untrained men, aged 25 ± 3 years, were analyzed and underwent a 6-week high load-resistance training protocol. The protocol was performed 3 days per week and consisted of 3 sets of 10 repetitions at 75% of 1-RM with a 3-minute rest in between sets. After these 6 weeks the participants underwent 12 months of detraining. Following this, the subjects performed 6 weeks of low load-resistance training to volitional fatigue, which consisted of 4 sets and was executed with 30% of 1-RM with a 3-minute rest between sets. The exercise performed was the bench press, and it was executed Monday, Wednesday, and Friday in both protocols. The subjects were measured for cross sectional area using an MRI scanner on the upper arm and chest. Results showed a similar increase in muscle cross sectional area between protocols with no significant difference between them. Researchers concluded that both 6 weeks of high load-resistance training and 6 weeks of low load-resistance training to volitional fatigue result in similar levels of skeletal muscle hypertrophy in the upper body. 

A study by Schoenfeld et al., 2014, evaluated muscular adaptations between bodybuilding type training — a training program using moderate-intensity loads and short rest intervals — and powerlifting type training — a training program using high-intensity loads and long rest intervals. All subjects were well-trained men in their respective disciplines. The subjects analyzed were 17 males — 9 in the bodybuilding type training and 8 in the powerlifting type training. These male volunteers were between the ages of 20 and 31 years and were considered experienced lifters with an average career of 4.2 ± 2.4 years. They were randomly assigned to either the bodybuilding or the powerlifting type training. Bodybuilding type training consisted of 8-12 repetitions per set that were performed with rest periods of 90 seconds between sets and exercises. Powerlifting type training consisted of 3 repetitions per set that were performed with rest periods of 3 minutes between sets and exercises. Both interventions had the same exercises and volume was equated between the two exercise programs. The study lasted 8 weeks and subjects were measured at baseline and at the end of the 8 weeks. Measurements were taken to determine both muscle thickness and muscle strength. Muscle thickness was measured using ultrasound imaging of the biceps brachii. The researchers found an increase in maximal strength and muscle thickness in both protocols. They also found no statistical difference in muscle thickness measurements between groups. They concluded that both bodybuilding and powerlifting type protocols promote similar increases in muscle size, however powerlifting-type training leads to a superior maximal strength. 

Another study compared the effects of a high intensity/low repetition resistance training protocol and a low intensity/high repetition resistance training protocol on muscle strength, size and bone mineral density in early postmenopausal, estrogen-deficient women (Bemben et al., 2000). Twenty-five early postmenopausal, estrogen-deficient women, aged 51.4 ± 5.5 years, completed the 6-month resistance training study. They were randomly assigned to either the high intensity/low repetition group, the low intensity/high repetition group, or the control group. Volume was equated among the two training groups. The high intensity/low repetition group performed 8 repetitions of 80% of 1-RM. The low intensity/high repetition group performed 16 repetitions of 40% of 1-RM. Resistance training was performed for 3 nonconsecutive days per week for 6 months. Subjects were measured for muscular strength, muscle cross-sectional area and bone mineral density. Muscle cross-sectional area was obtained by measuring the right biceps brachii and rectus femoris muscle groups by ultrasound. The researchers found rectus femoris cross-sectional area significantly increased for both resistance-training groups. They also found bicep brachii cross-sectional area significantly increased for the high intensity/low repetition group, and a trend to increase for the low intensity/high repetition group. The researchers concluded that both protocols were effective in improving muscular strength and size in postmenopausal women, and could be used interchangeably if certain intensities are contraindicated despite their differences in cross-sectional area results. 

Conclusions
The current literature suggests that there is no difference in hypertrophy of skeletal muscle between high repetition and low repetition resistance training protocols when using an intensity of load higher than 65% of 1-RM and equated in volume (Chestnut and Deocherty., 1999), (Campos et al., 2002), (Kraemer et al., 2004), (Schoenfeld et al., 2014). It is important to note that when intensities were lower than 65% of 1-RM the resistance training protocol was usually performed to failure, and the current literature shows that when resistance training is done to failure there is no difference in hypertrophy on skeletal muscle between high repetition and low repetition resistance training protocols despite intensity of load being lower than 65% of 1-RM (Masuda et al., 1999), (Leger et al., 2006), (Ogasawara et al., 2013). When resistance training protocols were not done to failure there was a difference in hypertrophy on skeletal muscle between the high repetitions and the low repetition resistance training protocol when intensities lower than 40% of 1-RM were used for the high repetition protocol and equated in volume (Campos et al., 2002), (Bemben et al., 2000). 

These data concur with previous research that suggests there is a minimum intensity of load required to see changes in skeletal muscle cross-sectional area, identified as 65% of 1-RM. From these studies we can conclude that in untrained or trained subjects where volume was equated, cross-sectional area in skeletal muscle did not differ between low or high repetition protocols. Volume loads dictated hypertrophy to a higher degree than inherited aspects of the protocol itself; however, there needs to be an intensity of load higher than 65% to see adaptations in skeletal muscle. It also appears that increased metabolic stress might not provide a relevant additive anabolic stimulus in comparison to the higher mechanic stress achieved with heavier loads. It is important to note that when resistance training is performed to failure it appears that an intensity of load higher than 65% is not required. Also, some of the studies where the high repetition resistance training was done to failure did not equate for volume (Masuda et al., 1999), (Ogasawara et al., 2013). This raises the question of whether training to failure or volume load dictate hypertrophy to a higher degree. 

Further research should focus on trained individuals and whether training to failure, an equated volume load, a higher volume load, or a mixture of these variables would maximize skeletal muscle hypertrophy. Studies should also focus on protocols longer than 10 weeks and on whether subjects are able to maintain the same intensities with either high repetitions or low repetitions for a macrocycle or whether low repetitions with a high intensity need to be properly periodized to equate for volume with bodybuilding type protocols. Studies regarding training to failure should also investigate how long this variable can be maintained or whether subjects will see decrements in performance or even overtraining during their first mesocycle. 

References
Bemben DA, Fetter NL, Bemben, MG, Nabavi N, Koh ET. Musculoskeletal responses to high-and low-intensity resistance training in early postmenopausal women. Med Sci Sports Exerc. 2000:32;1949-1957.

Campos GE, Luecke TJ, Wendeln HK, Hagerman FC, Ragg KE, Kraemer WJ, Luecke TJ, Toma K, Murray TF, Ratamess NA, Staron RS. Muscular adaptations in response to three different resistance-training regimens: specificity of repetition maximum training zones. Eur J Appl Physiol. 2002;88:50-60.

Chestnut JL, Docherty D. The effects of 4 and 10 repetition maximum weight-training protocols on neuromuscular adaptations in untrained men. J Strength Cond Res. 1999;13:353-359.

Housh DJ, Housh TJ, Weir JP, Weir LL, Johnson GO, Stout JR. Anthropometric estimation of thigh muscle cross-sectional area. Med Sci Sports Exerc. 1995;27:784-91.

Kraemer WJ, Nindl BC, Ratamess NA, Gotshalk LA, Volek JS, Fleck SJ, Newton RU, Hakkinen K. Changes in muscle hypertrophy in women with periodized resistance training. Med Sci Sports Exerc. 2004;36:697-708.

Léger B, Cartoni R, Praz M, Lamon S, Deriaz O, Crettenand A, Gobelet C, Rohmer P, Konzelmann M, Luthi, F, Russell A. Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol. 2006;576:923-33.

Masuda K, Choi JY, Shimojo H, Katsuta S. Maintenance of myoglobin concentration in human skeletal muscle after heavy resistance training. Eur J Appl Physiol Occup Physiol. 1999;79:347-52.

Ogasawara R, Loenneke JP, Thiebaud RS, Abe T. Low-load bench press training to fatigue results in muscle hypertrophy similar to high-load bench press training. Int J Clin Med. 2013;4:114-21.

Schoenfeld BJ. The mechanisms of muscle hypertrophy and their application to resistance training. J Strength Cond Res. 2010:24;2857-2872.

Schoenfeld BJ, Ratamess NA, Peterson MD, Contreras B, Sonmez GT, Alvar BA. Effects of different volume-equated resistance training loading strategies on muscular adaptations in well-trained men. J Strength Cond Res. 2014;28:2909-18.

Dr. Ponce is a licensed Doctor of Physical Therapy in Virginia.  He has experience working with collegiate athletes, weekend warriors, and orthopedic and neurological patients, and is passionate about increasing human performance and optimizing function.  He holds a bachelors in Human Nutrition Food & Exercise from Virginia Tech, a Masters in Exercise Science from Old Dominion University, and a Doctorate of Physical Therapy from Old Dominion University.  He has a Certified Strength and Conditioning Specialist certification from NSCA and over ten years of experience analyzing and correcting human movement patterns.  Dr. Ponce is also a proud veteran of the U.S. Army, serving as an infantryman in Operation Iraqi Freedom.  Follow Dr. Ponce on Instagram @poncephysiocoach.