The Latest on Hypertrophy

I decided to go to summer school because I want to expedite the process of my goal to obtain my M.S. in Exercise Science along with my PhD in Human Performance. Don’t feel sorry for me – my seminar class has been a blast so far!

The Science of Hypertrophy

The class has been incredible. In week one, I had to read two research articles regarding hypertrophy and watch a lecture online also regarding the latest in hypertrophy. The research was co-authored by my main professor, Dr. Alex Koch, who was also the lecturing professor in week one. The class is so much fun I decided to pass on the highlights to all of you to hopefully help you in your pursuits in coaching and/or your own training.

The research was published in the German Journal of Exercise and Sport Research.

The research article was “Skeletal Muscle Hypertrophy: Molecular and Applied Aspects of Exercise Physiology” by Victor Hugo F. Arantes, Dailson Paulucio da Silva, Renato Luiz de Alvarenga, and Augusto Terra (of the Biometry Laboratory, School of Physical Education and Sports, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil), Alexander Koch (from Exercise Physiology Laboratory, Lenoir-Rhyne University, Hickory, USA), and Marco Machado, Fernando Augusto Monteiro Saboia Pompeu (of the Laboratory of Physiology and Biokinetics, UNIG Campus V, Itaperuna, Rio de Janeiro, Brazil).

Before We Start

A big heads up! If you simply want to know the latest in hypertrophy training, you can skip down to the fourth question “regarding exercising programming.” I will have the bullets for you broken down into the different strategies. If you want to know the science behind the answers, read the whole article.

  • I want to define hypertrophy for all the people reading this who might not know. There are two types of hypertrophy: sarcoplasmic and myofibrillar. Sarcoplasmic hypertrophy is referring to the fluid of a muscle fiber’s sarcoplasm – especially the glycogen storage. Myofibrillar hypertrophy is the hypertrophy I will be referring to here today, which refers to an increase in the number of actin and myosin myofillaments. An increase in the number of myofilaments equals an increase in the size of the myofibrils they occupy, and ultimately equals an increase in the muscle’s cross-sectional area. The force a muscle can exert is related to its cross-sectional area rather than the volume or length. Simply put, we are talking about getting our muscles as huge as possible.
  • Rather than hormonal triggers, the article discusses that most myofibrillar hypertrophy comes from a multitude of mechanical mechanisms within the individual muscles. There is no doubt hormones aid in recovery and muscle mass, but that type of hormonal trigger is referring to the chronic state of one’s endocrine system and has very little to do with the acute state immediately following resistance training. I wouldn’t completely ignore the acute release of hormones because, based on some research from Bryan Mann, there are still some recovery benefits which are very important to overall results of an athlete’s macrocycle.
  • I want you guys to understand the difference in transcription and translation. Transcription takes place in the nucleus, and is the synthesis of mRNA (messenger ribonucleic acid which performs protein synthesis directed by DNA) from DNA (deoxyribonucleic acid, which holds your genetic coding that controls protein synthesis). Translation happens in the cytoplasm, and is the synthesis/creation of a protein in ribosomes created from the code written on the mRNA strand. Since myofilaments are the actin and myosin protein filaments, both transcription and translation are taking place.

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Digging into the Study

Here are some of the questions I had to answer, along with my answers:

1. The paper disputes “hormonal theory of skeletal muscle hypertrophy,” which was the prevailing scientific thought from the 1980s until very recently. Briefly summarize what hormonal theory is.

This theory suggested the acute elevation of testosterone, growth hormone, and IGF-1 that immediately follows resistance training was the main mechanism for hypertrophy. It appears the main problem is the elevated levels don’t stay around long enough (only 30 minutes or so) for long-lasting hypertrophy to take place.

2. What is the mechanistic target of rapamyosin (mTOR), and how does it relate to muscle growth?

mTOR is a main regulator of protein synthesis in skeletal muscle. When there are plentiful supplies of glycogen present, mTOR is going to be a major component of hypertrophy. When energy supplies for ATP are limited, its inhibition will actually cause atrophy to conserve energy.

This very statement is the reason trainers and coaches need to understand basic physiology. You can’t just train hard and heavy and expect results. ATP is needed for basic cellular function, so the body isn’t going to let you burn it up because you want to do some crazy workout after staying up all night and not eating. The body will actually inhibit the release of mTOR, and boom, you’re going the wrong way.

3. Describe the influence of the following factors on mTOR activity:

  • Nutritional factors: The paper doesn’t speak a lot about nutrition other than amino acids stimulate protein synthesis through the mTOR gateway. Furthermore, a couple of other natural compounds, ursolic acid and tomatidine were shown to have positive effects on protein synthesis. Although the article doesn’t state the effects on mTOR specifically, the research I looked at independently of this article stated both compounds positively effect mTOR signaling.

    There is one other factor regarding nutrition that can be induced from this article. Early in the article the author states the inhibition of mTOR is able to slow down or block other anabolic kinases preventing skeletal muscle hypertrophy. When exercising in a caloric deficit, mTOR is inhibited to conserve glycogen for ATP production. Therefore if your goal is hypertrophy, it would be recommended to not exercise in a caloric deficit or immediately supplement with added carbohydrates post-workout.
  • Hormonal factors: IGF-1 and growth hormone are shown to influence the muscle growth pathway up to a certain point. This anabolic function occurs through the PI3K/Akt/mTOR pathway. The author made it clear exercise-induced increases in IGF-1 or growth hormone did not increase the phosphorylation of PI3K (phosphatidylinositol 3-kinase), which is a catalyst during translation. Exercise-induced hormonal increases also had no effect on ribosomal protein S6 Kinase beta-1 (p70S6kinase), which is an enzyme that signals protein syntheses to take place in the ribosome.

    As far as testosterone – even though it’s well-known to induce substantial increases in skeletal muscle hypertrophy, exercise-induced testosterone is simply too short term (around 30 minutes). Recently it was discovered that “besides its effect through the androgen receptors, its effect on protein syntheses is dependent on the PI3K/Akt pathway.” This is the pathway for mTOR as well as other mechanisms for hypertrophy like the inhibition of myostatin, glucose metabolism, and transcription. However, higher levels of testosterone induced from exercise had no effect on mTOR levels or p70S6kinase. Therefore, acute fluctuations of testosterone induced from exercise had no affect on intracellular anabolic signaling.
  • Mechanistic factors: In your descriptions, please identify specific chemicals and their actions on the mTOR pathway.

    “The mechanical force produced by muscular contraction and captured by mechanoreceptors also produce protein synthesis,” but this is where the plot of the story takes a major turn, because this signaling takes place independent of the PI3K/Akt pathway and amino acids which are associated with IGF1 and testosterone. This process is at least partially associated with phospholipase D – an enzyme associated with the Z Line, the boundary at each end of the sarcomere, which is a critical site for mechanical force transmission. “Mechanistic factors also create activity of the zeta (ζ) isoform of di- acylglycerol kinase. Phospholipase D and the zeta (ζ) isoform of di-acylglycerol kinase are responsible for the release of phosphatidic acid, a lipid second messenger which is capable of causing anabolism through mTOR.” Phosphatidic acid also stimulates hypertrophy through p70S6K.

    The other aspect to be aware of regarding mechanistic factors is the transmembrane receptors in the costamere and myotendinous junction, which are responsible for focal adhesion kinase stimulation and phosphorylation/signaling of Akt, mTOR, and p70S6K. Based on the findings it appears the mechanistic factors create hypertrophy through different pathways than previously thought of such as hormones.

4. Regarding exercising programming, what does the evidence presented in this paper recommend as the best strategies to develop hypertrophy in terms of:

  • Exercise volume (sets x reps)
  • Intensity
  • Frequency
  • Rest periods
  • Eccentric-only training vs. concentric and eccentric
  • Speed of contraction

For each of these named program variables, provide the paper’s recommendations as well as a brief accounting of the evidence the authors use to support their recommendation.

    Volume – The answer is more complicated than a simple prescription. There was notable hypertrophy discovered with resistance exercise at only one set by Mitchell et al. (2012). However other studies showed differences in one and three sets depending on the muscle – for example Starkey et al (1996) reported that the medial thigh muscle only experienced significant difference in hypertrophy at three sets, so in that case one set wasn’t enough. Other studies showed more than double the increases in hypertrophy after multiple sets with ten sets being the maximum. However (Barbalho et al., 2019) showed no advantage to going over ten sets.

    The wise thing to do would be to start with one set and as hypertrophy slows down simply add a set in all the way up to ten sets. There are other variables not considered in the studies like multiple exercises per body part, which would likely create even more hypertrophy.

    Intensity – This is an interesting mechanism of hypertrophy. Most recently we have learned lower intensities at around 30% can invoke similar hypertrophic gains as higher loads between 75-80%. Burd et al. (2010b). In most studies volitional fatigue is one of the key factors to eliciting hypertrophy especially with the lighter loads. Most research will show greater muscle activation with the heavier loads (Schoenfeld, Contreras, Willard- son, Fontana, and Tiryaki-Sonmez, 2014; Jenkins et al., 2015a) FYI, two of these gentlemen are my friends. Schoenfeld believes the lighter loads led to greater Type I fiber gains, but that’s not proven.

    The important key in choosing intensity would be the understanding of your population. If you are coaching athletes, especially in a contact sport or one requiring massive amounts of power, muscle fiber recruitment – especially in the Type II fibers – is crucial. However if you were coaching a general fitness population or especially a geriatric population, I would recommend lower intensities as they are shown to signal similar hypertrophy gains. (Burd et al., 2010b) “discovered that lower loads require significantly greater total workout volume to induce the phosphorylation of anabolic kinases.”

    (Carroll et al., 2018, 2019) most recently showed that staying at a relative intensity from 65-90% as opposed to absolute failure will still induce substantial hypertrophy and in some cases superior. For athletes this might be the way to go because excessive volumes of muscle damage could be avoided allowing more adequate recovery and reducing the risk of injury.

    Frequency – Most of the studies showed very little change in muscle hypertrophy regardless of training frequency when volume was the same. There are individuals who appear to experience more hypertrophy from higher frequency. However, most studies have concluded frequency is of little value regarding skeletal muscle hypertrophy. (McLester et al., 2000; Candow and Burke, 2007; Gentil et al., 2015; Ribeiro et al., 2015; Saric et al., 2019). Based on a few studies including (Damas et al., 2019) in certain individuals higher frequency was able to produce more skeletal muscle hypertrophy. It’s for this reason frequency be chosen based on:

    • Lifestyle (work, schedule, family, etc)
    • Training age
    • Biological age
    • Available time to workout
    • Training goals

    Once again if the trainee is a novice, training a body part once per week is plenty for hypertrophy gains. Advanced individuals might consider maximizing frequency for an efficient way to increase total volume and to see if higher frequency elicits a better overall response.

    Rest periods – All the data points to longer rest periods if hypertrophy is the goal. Most studies compared three minutes versus one minute. Simply put, the longer rest periods allowed the trainees to perform more total volume to volitional fatigue or near failure leading to the “activation of anabolic kinases by intrinsic factors muscle contraction (mechanotransduction).” Buresh et al. (2009)

    Shorter rest periods induce more circulating growth hormone and testosterone, which led to coaches prescribing these short rest intervals to produce hypertrophy. However studies like this one (Miranda et al., 2007; Senna et al., 2009) clearly shows greater anabolic kinases from the longer rest intervals.

    Eccentric-only training vs. concentric and eccentric – It appears this mechanism of hypertrophy has the most room for growth. On one hand it appears that when eccentric contractions only are compared to eccentric and concentric contractions as in Eliasson et al. (2006)’s study only the maximal eccentric contractions elicited p70S6K and rpS6. In addition, force development was greater in maximal eccentric than in submaximal eccentric and maximal concentric contractions. So eccentric it is, right? Nope.

    In the outcomes recorded by Cadore et al. (2014), Farup et al. (2014), and Rahbek et al. (2014) “they recorded similar muscle growth when the eccentric and concentric workload wasn’t the same.” As well, Moore et al. (2012) demonstrated equal workload with the eccentric and concentric workloads and the hypertrophy was still the same. This is attributed to satellite cell content, which is only produced by concentric contractions. Based on the evidence dynamic contractions (eccentric and concentric) are most optimal for hypertrophy. This conclusion is backed up by this study (Schoenfeld, Ogborn, Vigotsky, Franchi, and Krieger, 2017).

    Speed of contraction – This is an area I hope to dive into much deeper with velocity based training. It appears based on the studies (Shepstone et al., 2005) that higher velocity eccentric contractions produced greater hypertrophy gains especially in the Type II fibers, making this finding even more important to athletes. However there was no difference in mTOR and p70S6K phosphorylation in the higher velocity and lower velocity sets when the workload was equal leading researchers to attribute the growth to greater acute “Z-line streaming” (myofibrillar remodeling) (Shepstone et al., 2005). Some speculate the higher velocity sets lead to higher volumes, which in turn leads to greater stimulation of the intrinsic factors of muscle contraction, such as the mechanotransduction pathway.

I hope this little article gives you some insight regarding training for hypertrophy. I knew I picked the right school when hypertrophy was the first topic. Dr. Alex Koch and Dr. Keith Leiting are both incredible professors who happen to love strength training. I can’t imagine studying under anyone else in the country. Thank you Lenoir-Rhyne University for giving this old guy a new trick to learn, and especially thank you Dr. Alex Koch for making this happen for me.

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