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What is hypertrophy?

This is an excerpt from Train Smarter, Not Longer by Patroklos \"Pak\" Androulakis Korakakis.

Muscle hypertrophy, also known as muscle growth, is a key objective in most resistance training programs aimed at enhancing strength, aesthetics, and, in some cases, sports performance (Krzysztofik et al. 2019). From recreationally active lifters aiming to “look better” to older adults wanting to improve their quality of life, most people who lift weights want to increase their muscle mass to some extent. Aside from helping you to look more muscular and potentially being better able to express strength, increases in muscle mass are vital for overall health and well-being, especially as you get older (Lee et al. 2018). However, this chapter will focus on the science around the minimum amount of training needed to see increases in muscle size that will help you to build an impressive physique while simultaneously obtaining the health benefits of hypertrophy.

Before we delve into the core of this chapter, let’s briefly examine the current mechanisms of muscle hypertrophy in an attempt to understand its actual cause. Although it seems logical that understanding the intricate details of muscle hypertrophy would help you fine-tune training variables for better results, the reality is more complex.

Understanding the mechanisms behind muscle hypertrophy requires the following:

1. Clear identification and verification of all known mechanisms backed by many studies in Petri dishes, animal models, and humans.
2. A deep understanding of physiology

You may be thinking, “What a delight, I am actually a physiology geek, and I can’t wait to dive into all the intricacies behind muscle hypertrophy!” Unfortunately, however, we are currently quite far from understanding all the intricacies underlying the mechanisms of muscle hypertrophy. Additionally, if you’re an outcome-focused lifter, which we assume you are since you’re reading this book, knowing exactly which molecular pathway is activated when you lift weights likely has little bearing on your future gains. By focusing on outcomes—in this case, muscle growth—and specifically on research that explores what best leads to those outcomes, you essentially learn which training approaches lead to better muscle growth. This is more practical than trying to piece together an extremely complicated puzzle and making training decisions based on a string of assumptions. Even if we knew exactly how muscle hypertrophy occurs, studies on humans examining different training approaches and which ones result in more muscle growth would still be your main go-to source of training information, as that’s what ultimately matters from a practical standpoint.

As it stands, the proposed “mechanisms” of muscle hypertrophy are mechanical tension, metabolic stress, and muscle damage (Wackerhage et al. 2019). In reality, since these suggested mechanisms initiate a sequence of processes that eventually result in larger muscle fibers, they are more accurately described as stimuli. Each of these stimuli activates specific cellular pathways that lead to building new muscle proteins and enlarging muscle fibers.

The most significant contributor to muscle growth is generally agreed to be mechanical tension, which involves forces that cause muscle fibers to contract and lengthen. These forces activate molecular pathways that lead to muscle protein synthesis.

The role of mechanical tension has been well-studied using various experimental designs. First, test tube studies have shown that tension increases myofiber size (Vandenburgh 1987). In animal models, different methods of exposing a muscle to tension, such as surgically removing one of the muscles responsible for a joint action (aka, synergist ablation) and thus forcing other muscles to compensate and produce more active tension, have consistently caused muscle growth (Murach et al. 2020). Finally, both resistance training and intense stretching approaches, which expose muscles to tension (both active and passive), build muscle (Warneke et al. 2022). Conversely, a lack of movement, such as during long periods of inactivity, results in decreased protein synthesis and thus muscle atrophy. Importantly, all of these study models have their weaknesses. Lab studies cannot replicate complex, real-world biological systems; conversely, resistance training approaches in humans don’t just apply tension to the muscle but may also involve other stimuli for muscle hypertrophy that we’ll subsequently discuss. Additionally, there is a long list of complicating factors that could also influence the muscle growth response in living organisms. However, overall, most research supports tension as a main stimulus for muscle hypertrophy than any other potential cause.

Metabolic stress is another proposed “mechanism” of muscle hypertrophy, although the current evidence around its importance and actual involvement is mixed (Schoenfeld 2013). Metabolic stress occurs during high-intensity exercise when there is an accumulation of metabolites such as lactate, inorganic phosphate, and hydrogen ions (Chin 2005). Metabolites are simply by-products of energy metabolism, a process that occurs continuously to allow your muscle fibers to contract and generate movement and force. Metabolic stress is maximized during exercise that relies heavily on anaerobic glycolysis for energy production, characterized by a reduced phosphocreatine (PCr) concentration, elevated lactate levels, and a low pH.

In humans, the potential role of metabolic stress in muscle hypertrophy is supported by some of the literature looking into blood flow restriction (BFR), which involves using cuffs or bands to partially restrict blood flow to muscles. BFR is performed so that arterial inflow remains relatively intact (although somewhat impeded) while inhibiting venous outflow. This results in blood pooling, reduced oxygen (hypoxia), increased reliance on anaerobic metabolism, and buildup of metabolic byproducts like lactate in the area below where blood flow is restricted (Takarada, Takazawa, and Ishii 2000). Research has shown that even without resistance training, the use of BFR somewhat reduced muscle atrophy of the knee extensors during bedrest (Takarada, Takazawa, and Ishii 2000). Additionally, when BFR and low-intensity aerobic exercise are combined, there is an increase in cross-sectional area in the quads and hamstrings (Abe, Kearns, and Sato 2006). It’s worth noting that dozens of metabolites have been linked to resistance training, but their effects on muscle growth have largely gone unstudied.

Lastly, muscle damage has traditionally been thought to play a role in muscle hypertrophy, but much like metabolic stress, muscle damage is an umbrella term that covers many physiological responses. In fact, even after hundreds of studies on the topic, the exact causes of muscle damage remain unclear (Damas, Libardi, and Ugrinowitsch 2018). Muscle damage, caused primarily by eccentric (lengthening) contractions, triggers inflammatory responses and activates satellite cells, which are needed to repair and grow muscle tissue (Schoenfeld 2010). Some of the physiological changes associated with muscle damage include z-band streaming, loss of muscle sarcomeric proteins, an increase in inflammatory cytokines after exercise, and more. Since directly assessing some of the effects of muscle damage is invasive and can require multiple biopsies, researchers often use indirect markers to assess muscle damage such as changes in performance, post-exercise muscle swelling, and even delayed-onset muscle soreness. As it stands, muscle damage, at least in mild to moderate degrees, should be viewed as a partial or contributory stimulus to hypertrophy, as it may influence muscle growth through the inflammatory process and its influence on satellite cell activity (Bazgir et al. 2017). However, too much muscle damage is clearly counterproductive—it impairs the ability to train effectively, and ineffective training leads to poor results.

Overall, the deeper you dive into the “hows and whys” behind muscle hypertrophy, the more complex things get, and the more you realize that we still have a great deal to learn. As it stands, we’re still not exactly sure what the entire puzzle of muscle growth looks like, but that’s not necessarily a major limiting factor in designing effective resistance training programs. As mentioned earlier, by focusing on research that has directly examined the effect of specific variables on muscle building, we can determine the minimum effort needed to make meaningful gains, how hard you should train, and so on. This brings us to the core principles for hypertrophy. These principles are likely the most important factors to consider if you’re trying to grow muscle and will allow you to have substantial control over your training outcomes, despite all the questions that still remain regarding the exact mechanisms of muscle growth.

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