Training for Hypertrophy: the Latest Research on Muscle Training Response

Training for Hypertrophy

If you spend a lot of time at the gym, you know that the biggest guys are not necessarily the strongest. While muscle size is impressive, especially if you want to compete as a bodybuilder, extra bulk is not always functional, and too much mass can interfere with performance in sports that require speed, agility and flexibility.

Of course, there are certain sports where high amounts of lean body mass are desirable. Some positions in American football, certain types of wrestling and combat sports, powerlifting, and throwing events in track and field all demand high muscle mass to withstand opposing forces.

For the average Joe, muscle mass is important for performing everyday activities, supporting the joints and providing balance and stability. As humans age, sarcopenia (wasting of lean mass) can reduce functional movement and stability, increasing the risk of falls and injury. Beyond basic functionality, extra muscle mass has cosmetic appeal that may provide social benefits and boost self-esteem for some. And lean mass increases your metabolism, helping you manage your body weight.

There are many conflicting theories about how to best achieve the muscle response you want from your workouts. Some are rooted in gym lore, while others can be backed up with research. We dug deep into the literature to find the latest research on resistance training for increased muscle mass, aka hypertrophy.

What Causes Muscle Hypertrophy?

What Causes Muscle Hypertrophy?

Put simplistically, if you want bigger muscles, you have to increase the size of the individual muscle cells. This can be achieved in two ways: by increasing sarcoplasmic volume and by increasing myofibril density.

Sarcoplasm is a watery solution within the muscle cells that contains ATP, phosphagens, glycogen, myoglobin and enzymes, all needed for muscle function and repair. Glycogen, the storage form of glucose, and phosphocreatine (PC) are two substrates needed to regenerate ATP, necessary for muscle contraction. Regular training that depletes ATP, PC and glycogen leads to increased storage of those substrates, which in turn increases the volume of sarcoplasmic fluid. Sarcoplasmic hypertrophy does not contribute to increased muscle strength, but it does contribute to overall muscle size.

Myofibrils are contractile proteins that make up the muscle itself. There are two types of myofibrils, actin and myosin. Resistance training promotes the growth and multiplication of myofibrils, leading to increased muscle fiber density and increased strength.

To get a hypertrophic response, you must consistently train your muscles with the right volume, frequency and intensity of resistance exercise to stimulate the necessary training adaptations in the sarcoplasm and myofibrils.

Fundamental Principles of Resistance Training

Fundamental Principles of Resistance Training

The science of resistance training has evolved over the past few decades, but most of the fundamentals remain constant, and revolve around a few key principles:

  • Overload: The most basic and overriding principle for building both size and strength is overload, the process of subjecting your body to force loads greater than it is accustomed to handling. Overloading your muscles evokes an adaptation response of increased strength and size. The adage “no pain, no gain” derives from the discomfort associated with overload. Progressive overload is the practice of gradually and progressively increasing load to make additional ongoing gains in muscle size and strength.
  • Volitional fatigue: Lifting progressively heavier weights is not enough to reach optimal gains. You have to completely deplete your muscles’ capacity to regenerate ATP in a single weight lifting set, taking your muscles to the point of failure. This causes your cells to adapt by increasing glycogen and phosphocreatine stores to regenerate ATP.
  • Time under tension: The speed of each repetition plays a huge role in your total exercise workload. Slower contractions eliminate momentum and gravity from the equation, making your muscles do all the work. But this principle goes beyond speed. During a single repetition, muscle contraction goes through three phases: concentric (where the muscle shortens against the force of gravity), isometric (where there is a brief period of muscle tension without movement) and eccentric (where the muscle lengthens with tension in the direction of gravity). Guidelines for muscle hypertrophy established by the American College of Sports Medicine (ACSM) recommend 3-4 sets of 8-12 repetitions. The recommended speed ratio per rep is 4 (eccentric): 2 (isometric): 1 (concentric).
  • Training volume: High training volume is key to muscle hypertrophy. Its formula is reps x sets x weight lifted. For a given isolated muscle or muscle group, bodybuilders typically perform 4 to 6 sets of 6 to 12 repetitions, using a load that causes volitional fatigue within that repetition range. For hypertrophy, ACSM guidelines recommend weight loads of 70-85% 1RM (max amount you can lift one time), with 3-6 sets of 8-12 reps. Rest 2-3 minutes between sets.
  • Training frequency and recovery: The work you do in the gym challenges, depletes and damages muscle fibers. Resting between sets gives your muscles time to regenerate ATP for the next set. During the between-workout recovery period, muscle fibers are repaired and enhanced, and substrates are replenished with higher sarcoplasmic storage volumes of glycogen, PC and enzymes. After a challenging training session, the targeted muscles need from 48 to 72 hours or longer to heal and recover. Most bodybuilders do training splits throughout the week, to give muscles a longer recovery period. A popular approach is to train upper body “push” muscles (chest, triceps and shoulders) on day one, legs and abs on day two, and upper body “pull” muscles on day three.

Recent Studies on Hypertrophy Training

Recent Studies on Hypertrophy Training

There are literally thousands of studies on resistance training, many of them looking for a definitive formula to get the best training response for size and strength. Here is a brief summary of three of the most recent:

  • Turn up the volume: In a 2019 study by Schoenfeld et al., researchers looked at the impact of training volume on muscle adaptation in men who regularly weight train. The 34 study participants were divided into three training groups: low volume (1 set of each exercise per day), moderate volume (3 sets per exercise per day), and high volume (5 sets per exercise per day). All participants exercised on 3 non-consecutive days per week for 8 weeks. All groups saw similar significant increases in muscle strength and endurance. Ultrasonography was used to assess muscle size pre- and post-intervention. All 3 groups saw increases in muscle thickness, but the high volume group had significantly greater increases in muscle size, pointing to training volume as a key factor for muscle hypertrophy.
  • The short and long of it: In another study, Goto et al. (2019) wanted to investigate whether range of motion during resistance training would affect the hypertrophy response. Study participants were 44 young men who did regular resistance training. Half were placed in a full range of motion group (0º to 120º) and half in a partial ROM group (45º to 90º). Both groups performed barbell triceps extensions, 3 sets of 8 reps at 8RM, three times a week for 8 weeks. At the end of the study, both groups increased muscle size, but the limited ROM group had significantly larger gains in triceps cross-sectional area (48.7 ± 14.5%, compared to 28.2 ± 10.9% for the full ROM group).
  • Mixed review: Researchers Schoenfeld and Grgic (2020) were also interested in the impact of range of motion on muscle adaptation. They conducted a review of the literature to see which studies had been done, and what conclusions had been drawn. They looked at six studies, four of which involved lower limb training, and two involving upper limb training. They concluded that full range of motion had greater hypertrophic effects on lower limb muscles than partial ROM. Data on upper body training was conflicting. The researchers suggested that response to ROM training may be muscle-specific.

Occlusion Training

Occlusion Training

Occlusion training, also called blood flow restriction training, (BFRT), is used in rehab to stimulate muscle hypertrophy at substantially lower weight loads. The idea is to stimulate muscle growth while protecting damaged tissues that are in the process of healing.

Here’s how BFRT works:

  • An occlusion cuff similar to a blood pressure cuff is place on the upper arm or upper thigh to limit the amount of blood flowing to the muscles. For the upper body, 50% occlusion is recommended. Eighty percent occlusion is recommended for the lower body.
  • Resistance is set at 20-35% 1RM (compared to 70%+ for traditional training).
  • The subject performs four exercise sets, consisting of 30, 15, 15 and 15 repetitions, respectively. A 30-second rest is taken between sets. The concentric:eccentric ratio is 2:2 seconds.

The premise underlying occlusion training is that soft tissue damage is spared, and muscle fiber type is selective. Damage to the sarcomeres, the structural units of myofibrils, causes hypertrophy during traditional training, as hypertrophic traits are enhanced in the recovery phase.

In BRFT, tissue damage is minimal due to lighter training loads. But restricted oxygen flow essentially takes oxidative Type I slow twitch fibers out of the picture, and anaerobic Type II fast twitch fibers are optimally recruited. In addition, growth hormone secretion is 170% higher after BRFT, which increases collagen synthesis, thereby protecting tendons and muscle collagen structures.

Optimize Your Performance with NYDNRehab Physical Therapy in NYC

At the end of the day, muscle size is not as important as overall performance for any athlete, and the only way to reach your peak is to measure your progress. The sports medicine team at NYDNRehab uses advanced technologies and innovative training methods to diagnose, assess, prescribe and measure muscle responses to training interventions.

State-of-the-art equipment coupled with experience and up-to-date knowledge make NYDNRehab the best clinic for physical therapy in Manhattan, for performance enhancement and injury rehab. Contact us today, and discover your peak performance potential at NYDNRehab


Goto, Masahiro, et al. “Partial range of motion exercise is effective for facilitating muscle hypertrophy and function through sustained intramuscular hypoxia in young trained men.” The Journal of Strength & Conditioning Research 33.5 (2019): 1286-1294.
Schoenfeld, Brad J., et al. “Resistance training volume enhances muscle hypertrophy but not strength in trained men.” Medicine and science in sports and exercise 51.1 (2019): 94.
Schoenfeld, Brad J., and Jozo Grgic. “Effects of range of motion on muscle development during resistance training interventions: A systematic review.” SAGE Open Medicine 8 (2020): 2050312120901559.

About the Author

Dr. Lev Kalika is clinical director of NYDNRehab, located in Manhattan. Lev Kalika is the author of multiple medical publications and research, and an international expert in the field of rehabilitative sonography, ultrasound guided dry needling and sports medicine Dr. Kalika works with athletes, runners, dancers and mainstream clients to relieve pain, rehabilitate injuries, enhance performance and minimize the risk of injuries. His clinic features some of the most technologically advanced equipment in the world, rarely found in a private clinic.


In this instance, an athlete was originally diagnosed with minor quadriceps muscle strain and was treated for four weeks, with unsatisfactory results. When he came to our clinic, the muscle was not healing, and the patients’ muscle tissue had already begun to atrophy.

Upon examination using MSUS, we discovered that he had a full muscle thickness tear that had been overlooked by his previous provider. To mitigate damage and promote healing, surgery should have been performed immediately after the injury occurred. Because of misdiagnosis and inappropriate treatment, the patient now has permanent damage that cannot be corrected.

The most important advantage of Ultrasound over MRI imaging is its ability to zero in on the symptomatic region and obtain imaging, with active participation and feedback from the patient. Using dynamic MSUS, we can see what happens when patients contract their muscles, something that cannot be done with MRI. From a diagnostic perspective, this interaction is invaluable.

Dynamic ultrasonography examination demonstrating
the full thickness tear and already occurring muscle atrophy
due to misdiagnosis and not referring the patient
to proper diagnostic workup

Demonstration of how very small muscle defect is made and revealed
to be a complete tear with muscle contraction
under diagnostic sonography (not possible with MRI)


Complete tear of rectus femoris
with large hematoma (blood)


Separation of muscle ends due to tear elicited
on dynamic sonography examination

Buy now 3D Gait
Payment Success
Request Telehealth Request Telehealth Request in office visit Book now