Muscle Hypertrophy: Intro

What is Muscle Hypertrophy?

If you are new to strength training or performance, you probably have heard of the term hypertrophy. Hypertrophy is the enlargement of an organ or tissue. Generally, when someone refers to hypertrophy they are referring to increasing total muscle size/weight and therefore total body size/ weight. It is important to understand that exercise induced changes in muscle size do not necessarily induce changes in muscle strength (2). The principle of specificity dictates that some strategies will promote greater hypertrophy than others; we will discuss methods to maximize muscle hypertrophy.

What Causes Hypertrophy?

The metabolic basis for muscle hypertrophy occurs when muscle protein synthesis exceeds the rate of muscle protein break down. In the long term, a positive net protein balance may result in muscle hypertrophy while a negative net protein balance may result in muscle atrophy. This is largely due to four factors: 1) exercise, 2) nutrition, 3) hormonal status, and 4) the interaction between these factors. Understand that the majority of muscle hypertrophy comes from the interaction between exercise and hormonal as well as nutrition and hormonal status.

We will not be discussing hormones or hormonal interactions because hormones are produced in response to a stimulus (exercise or nutrition). It makes more sense to discuss best practices in creating a hypertrophic stimulus; focusing on the things we can control (diet and exercise), rather than focus on the specific hormonal outcomes (cellular upregulation of mTOR or JNK) that are consequences of diet and exercise.

Types of Muscle Hypertrophy:

There are several types of muscle hypertrophy: 1) hyperplasia, 2) myofibril hypertrophy, and 3) sarcoplasmic hypertrophy.

Hyperplasia is increasing the number of muscle fibers in a given muscle. This usually occurs when a singular muscle fiber splits. So the amount of muscle has not changed, but the number of muscle fibers increases. The effects of hyperplasia are minimal in humans; minimal to the extent that there is scientific debate as to whether hyperplasia even occurs in humans (3). However, given that trained individuals have a higher number of muscle fibers compared to untrained individuals, we think it is likely hyperplasia occurs although it may contribute minimally to hypertrophy or be insignificant.

During hypertrophy, contractile elements enlarge and the extracellular matrix expands to support growth. Myofibril hypertrophy is increasing the proportion of muscle fibers or contractile units within a muscle. When skeletal muscle is subjected to an overload stimulus, it causes perturbations in myofibers that ultimately leads to an increase in the size and amounts of the myofibrillar contractile proteins actin and myosin, and the total number of sarcomeres in parallel (1). Sarcoplasmic or myoplasmic hypertrophy is when there is an increase in various non-contractile elements and fluids. This increase in non-contractile elements is primarily due to metabolic stimuli produced as a result of resistance training. Sarcoplasmic hypertrophy may result in greater muscle bulk without concomitant increases in strength (1).

Mechanics of Muscle Hypertrophy:

Unlike other cells, muscle tissue does not undergo significant cell replacement throughout life. Therefore instead of mitosis (one cell splitting into 2 cells), muscle tissue increase in size and volume by adding additional proteins and components.

Hypertrophy is thought to be mediated by the activity of satellite cells, these “myogenic stem cells” are normally dormant but become active when a sufficient stimulus is imposed. Once aroused, satellite cells proliferate and ultimately fuse to existing cells or among themselves to create new myofibers, providing the precursors needed for repair and subsequent growth of new muscle tissue (1).

1. Satellite cells donate extra nuclei to muscle fibers, increasing the capacity to synthesize new contractile proteins.

2. The myonucleus regulates mRNA production for a finite sarcoplasmic volume and any increases in fiber size must be accompanied by a proportional increase in myonuclei.

3. Myonuclei express various muscle regulatory signaling proteins that aid in muscle repair, regeneration, and growth.

Major factors that stimulate satellite cells are:

1. Mechanical tension produced both by force generation and stretch is considered essential to muscle growth. Specifically, mechanical overload increases hypertrophy while unloading causes atrophy (1,4). Passive tension produces a hypertrophic response that is fiber-type specific, with an effect seen in fast-twitch but not slow-twitch fibers (Prado et al. 139). Although mechanical tension can produce hypertrophy, certain strength training routines employing high degrees of muscle tension but mostly induce neural adaptations without resultant hypertrophy (1,4).

2. Muscle damage can be specific to just a few macromolecules of tissue or result in large tears, as well as damage the supportive connective tissue (1). Muscle damage has been linked to delayed onset muscle soreness and a short term inflammatory response. Part of that inflammation is white blood cells removing cellular damage but they also help activate satellite cells into multiplying and fusing to new muscle fibers (4).Moderate to high loads during the eccentric movements is associated with significant exercise induced muscle damage, which have been associated with a hypertrophic response (1).

3. Metabolic stress has a significant hypertrophic effect, either in a primary or secondary manner (1). The anabolic role of exercise-induced metabolic stress relies on anaerobic glycolysis for ATP production, which results in the subsequent buildup of metabolites (1). Muscle ischemia (blood occlusion training) has also has been shown to produce substantial metabolic stress (1,4). Therefore a hypoxic muscle tissue (without sufficient oxygen for aerobic production of ATP) may be ideal for stimulating hormone production and satellite cells (1).

1. Schoenfeld, Brad J. “The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training.” Journal of Strength and Conditioning Research, no. 10, Ovid Technologies (Wolters Kluwer Health), Oct. 2010, pp. 2857–72. Crossref, doi:10.1519/jsc.0b013e3181e840f3. https://journals.lww.com/nsca-jscr/Fulltext/2010/10000/The_Mechanisms_of_Muscle_Hypertrophy_and_Their.40.aspx

2. Loenneke, J. P., Buckner, S. L., Dankel, S. J., & Abe, T. (2019). Exercise-Induced Changes in Muscle Size do not Contribute to Exercise-Induced Changes in Muscle Strength. Sports Medicine, 49(7), 987–991. https://doi.org/10.1007/s40279-019-01106-9. https://pubmed.ncbi.nlm.nih.gov/31020548/

3. Kelley, G. (1996). Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis. Journal of Applied Physiology, 81(4), 1584–1588. https://doi.org/10.1152/jappl.1996.81.4.1584. https://journals.physiology.org/doi/pdf/10.1152/jappl.1996.81.4.1584

4. Hawke, T. J., & Garry, D. J. (2001). Myogenic satellite cells: physiology to molecular biology. Journal of Applied Physiology, 91(2), 534–551. https://doi.org/10.1152/jappl.2001.91.2.534.