Muscle Hypertrophy

New insights and training recommendations.

By Aaron Bubbico
Oct 18, 2011

Muscle hypertrophy, or muscle cell enlargement, is a topic of great debate and interest in all fields of health, fitness and sports. How the body responds to muscular overload to elicit muscle growth is still under much scientific investigation.

Many types of training educe muscle hypertrophy. This is evidenced by the fact that athletes in numerous sports exhibit wonderful muscular development even though they follow different training protocols. With this in mind, it makes sense to examine contemporary understandings of muscle hypertrophy and highlight some effective training approaches.

Muscle Hypertrophy

Muscle hypertrophy is an increase in muscle fiber size, observed when the muscle achieves a larger diameter or thickness. New muscle fibers are not created during hypertrophy in humans, although Paul and Rosenthal (2002) note new-fiber creation has been observed in some animal studies, owing to unique structural differences in muscle anatomy between species.

With muscle hypertrophy at the cellular level in humans, the actin and myosin contractile proteins increase in size and number (Schoenfeld 2010). In addition, as Schoenfeld explains, there is an increase in the fluid (sarcoplasm) and noncontractile connective tissues interspersed within muscle, a concept collectively referred to as sarcoplasmic hypertrophy. In eccentric training, which overloads the muscle during lengthening, muscle cells also add sarcomeres (the smallest functional unit of muscle fibers) longitudinally, thus adding length to the muscle fiber as well (Proske & Allen 2005).

It is important to note that strength gains made in the first couple of months of training are primarily neural adaptations (Schoenfeld 2010). Gabriel, Kamen and Frost (2006) explain that in early training phases, the muscle is acquiring greater neural input, referred to as neural drive. Underlying this greater neural input are the motor unit recruitment patterns of muscle fiber types (see Figure 1 for an explanation of motor unit recruitment). Each motor unit represents a single nerve and the many muscle fibers it innervates.

Satellite Cells, Cytokines and Hormones: Exploring New Insights Into Muscle Hypertrophy Mechanisms

Satellite cells are the “stem” cells of skeletal muscle (Schoenfeld 2010). Like stem cells, satellite cells have unique physiological characteristics and functions. They can be characterized as small, mononuclear cells located between the basement membrane of a muscle fiber (called the basal lamina) and the sarcolemma (the polarized plasma membrane). They function to repair damaged muscle tissue and trigger skeletal muscle growth after any type of overload. Once satellite cells are stimulated by muscular overload, they fuse to the muscle fiber and facilitate muscle hypertrophy by forming a new nucleus. Uniquely to human physiology, muscle fibers have numerous nuclei. Each nucleus is responsible for a finite area of volume and tissue within the muscle fiber, a concept called myonuclear domain (Schoenfeld 2010).

The exercise-induced stimulus from resistance exercise activates a complex response of cellular messaging pathways, cytokines and hormones that set muscle hypertrophy in motion (see Figure 2). Three distinct messaging pathways (calcium-dependent pathway, mitogen-activated protein-kinase pathway and rapamycin pathway) shift the cell into a protein synthesis condition while also inhibiting protein breakdown (Schoenfeld 2010). Cytokines are messaging proteins from the immune system that interact with specialized receptors on muscle to promote tissue growth. Significantly, some anabolic (muscle growth–promoting) hormones—including insulin-like growth factor, testosterone and growth hormone—play a primary role in promoting hypertrophy (Schoenfeld 2010).

Some Distinctive Training Methods That Promote Hypertrophy

Schoenfeld (2011) explains that even though direct research is lacking, several bodybuilding training methods appear to promote muscle growth because they incite one or all of the factors that activate hypertrophy in muscle (see the sidebar “5 Questions About Muscle Hypertrophy”).

Descending-Weight or Drop Sets

Countless variations are possible on descending-weight or drop sets. For example, an exerciser might do 8 repetitions of a dumbbell lateral raise with 35 pounds to failure, put those dumbbells down and complete 8 repetitions with 25 pounds to failure, and then drop to 8 repetitions with 15 pounds to failure. Depending on the exerciser, a sequential drop of 10%–25% in weight would be appropriate for this technique.

Alternating Rest Periods Between Multiple Sets

Typically, three types of rest periods are used in resistance exercise: short (30 seconds or less), moderate (60–90 seconds) and long (3 minutes or more) (Willardson 2006). Short rest periods may cause a significant amount of metabolic stress, which is now believed to be a potent stimulator for hypertrophy (Schoenfeld 2011). However, with shorter rest periods (between multiple sets) it is harder to obtain the higher workloads needed to really overload muscle. By alternating rest periods (between multiple sets), the exerciser may be able to create more metabolic stress in some sets and more mechanical tension in others, both of which promote hypertrophy.

Eccentric Training

As highlighted by Schoenfeld (2011), a significant amount of research has shown that eccentric training leads to great gains in muscle hypertrophy (for a complete review of eccentric training, read “Eccentric Training” in October 2010 IDEA Fitness Journal). One popular eccentric training technique is the “supramaximal technique,” in which the client lifts a weight (with the aid of a personal trainer) that is 105%–125% of that person’s normal load and then lowers the weight eccentrically in 3–4 seconds.

Forced Repetitions

With spotting from a personal trainer, the client completes 2–4 extra repetitions after reaching momentary muscular fatigue during a set.


Supersets, or paired sets, consist of any two sets performed in sequence (with no rest between exercises). Schoenfeld (2011) notes that the metabolic stress induced by this technique may be responsible for the hypertrophic gains it can produce. Possible superset strategies (and examples of each) include agonist/antagonist (e.g., biceps curl and triceps extension), opposite action (e.g., chest flye and seated row), upper body/lower body (e.g., chest press and leg press), lower body only (e.g., lunge and heel raise) and upper body only (e.g., flye and chest press).

Concluding Comments

It is remarkable to see how scientists are now beginning to understand and explain many hypertrophy techniques that have been used for decades. The physiological responses to training vary according to a person’s age, fitness level, hormonal levels, gender and tolerance for mechanical overload. It is always a major responsibility of the personal trainer to assess what strategies to use and how much training is best to help clients attain their muscular fitness goals.

Figure 1. Motor Unit Recruitment

Motor units for the most part are recruited in order of increasing size, because the size (in diameter) of the motor unit is directly related to its force-producing capability. A lighter force demand placed on the muscle will emphasize activation of slow-twitch type 1 fibers (see A). As the force on muscle increases, the fast-twitch type IIa fibers are activated with the help of type I fibers (see B). With the most challenging demands of muscle, the most powerful (and largest) type IIb fibers are triggered to fire, with the help of type I and type IIa fibers (see C).

Source: Enoka 1995. Adapted from an illustration by Lyman Dally.

Figure 2. Mechanisms of Muscle Hypertrophy

Source: Schoenfeld 2010.

5 Questions About Muscle Hypertrophy

1. What are the most important factors for promoting hypertrophy?

Mechanical tension, muscle damage and metabolic stress are the three primary factors that promote hypertrophy from exercise (Schoenfeld 2011). Mechanical tension is directly related to exercise intensity, which is the key to stimulating muscle growth. Muscle damage—leading to muscle soreness from exercise training—initiates an inflammatory response, which activates satellite cells’ growth processes. And metabolic stress, a result of the byproducts of anaerobic metabolism (i.e., hydrogen ions, lactate, inorganic phosphates), is now also believed to promote hormonal factors leading to muscle hypertrophy.

2. Which tend to show hypertrophy faster: the upper extremities or the lower extremities?

The upper extremities tend to show more growth faster than the lower extremities (Schoenfeld 2011).

3. What is the ideal intensity for maximizing hypertrophy?

Maximal growth occurs with loads between 80%–95% of 1-repetition maximum (Fry 2004).

4. How do weightlifters, power lifters and bodybuilders differ in their hypertrophic responses to training?

According to Fry (2004), weightlifters and power lifters show more favorable hypertrophy of type II (fast-twitch) muscle fibers, whereas bodybuilders appear to have comparable hypertrophy in both type I (slow-twitch) and type II muscle fibers.

5. Which are better for developing hypertrophy: single- or multiple-joint exercises?

Multijoint exercises have been shown to produce larger increases of anabolic hormones compared with single-joint exercises and thus should be prioritized (Hansen et al. 2001).


Enoka, R.M. 1995. Morphological features and activation patterns of motor units. Journal of Clinical Neurophysiology, 12 (6), 538–59.
Fry, A.C. 2004. The role of resistance exercise intensity on muscle fibre adaptations. Sports Medicine, 34 (10), 663–79.
Gabriel, D.A., Kamen, G., & Frost, G. 2006. Neural adaptations to resistive exercise: Mechanisms and recommendations for training practices. Sports Medicine, 36 (2), 131–49.
Hansen, S., et al. 2001. The effect of short-term strength training on human skeletal muscle: The importance of physiologically elevated hormone levels. Scandinavian Journal of Medicine & Science in Sports, 11 (6), 347–54.
Paul, A.C., & Rosenthal, N. 2002. Different modes of hypertrophy in skeletal muscle fibers. The Journal of Cell Biology, 156 (4), 751–60.
Proske, U., & Allen, T.J. 2005. Damage to skeletal muscle from eccentric exercise. Exercise and Sports Science Reviews, 33 (2), 98–104.
Schoenfeld, B.J. 2010. The mechanisms of muscle hypertrophy and their application to resistance training. Journal of Strength and Conditioning Research, 24 (10), 2857–72.
Schoenfeld, B.J. 2011. The use of specialized training techniques to maximize muscle hypertrophy. Strength and Conditioning Journal, 33 (4), 60–65.
Willardson, J.M. 2006. A brief review: Factors affecting the length of the rest interval between resistance exercise sets. Journal of Strength Conditioning Research, 20 (4), 978–84.


Aaron Bubbico

Aaron Bubbico is working on his master’s degree in exercise science at the University of New Mexico, Albuquerque (UNM). He is the owner and operator of Quality Fitness Training. His research interests include eccentric load training, hypertrophic adaptations and mechanisms, and periodization.

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