Understanding Muscle Hypertrophy

Understanding Muscle Hypertrophy


The key role of hypertrophy is first mentioned in 1804: "If I always willingly use the right arm, and if I always resist the left arm, then the size of the bone of the right arm will grow, although the length of my arm will be reduced." A hundred years later, a distinguished anthropologist wrote: "Ah nature, exercise bones, muscles and the heart, so it is their growth and not grinding will make them stronger." Not so long after, exercise psychologist wearily pointed out: "Building on the skeleton on the basis of a normal body is the goal of regular physical activity (homeostasis development)," to which we have to add an accessory goal, that is adaptation to overload, leading in the distant muscles to increase the density of capillaries and production of oxidative enzymes.

To many practitioners of muscle physical training, "hypertrophy", the Greek word for over-feeding or excessive nourishment, is the key to success. But, during the submaximal effort, not only hypertrophy is concerned, but also hyperplasia, and it is their mutual contribution, also with the modification of the anatomical structure, that leads to desired improvement during the maximal effort.

Factors influencing muscle hypertrophy

Amino acids can be used to obtain energy during physical exercise when carbohydrate stores are low, and their content is influenced by the amount and intensity of the exercises performed. Furthermore, hormones can exert their influence on muscle by interrupting the anabolic effects of insulin. However, the growth hormone (GH) also has important functions on some of these hormones, since it has characteristics in the anti-insulin effect expressed by anti-insulin resistance and a counter-regulatory role. Insulin-like growth factor I (IGF-I) is considered to be one of the main mediators of the GH effects. IGF-I is linked to binding proteins for insulin-like growth factors (IGFBPs), and the role of the IGFBP-3 complex has the property of prolonging the half-life of IGF-I and inducing its function in the musculoskeletal system, enhancing the physiological conditions. Furthermore, high levels of IGF-I minus acid-type insulin-like factors (IGF-II) are achieved through the action of the GH and are known to increase muscle hypertrophy under the influence of the GH. Therefore, IGF-I occupies a crucial position in the GH-induced muscle hypertrophic process.

To appropriately prescribe resistance training aimed at increasing muscle hypertrophy, some factors need to be considered. As we described earlier, the type of mechanical stimuli and muscle contraction that are more efficient for muscle hypertrophy, absence of exercise along with comparative muscle atrophy, we will describe later, some factors that must be considered for the hypothesis that the muscle hypertrophy process. Hormones have a catabolic role in the process of muscle hypertrophy, and they, along with exercise, are able to modify the hypertrophic response. Elevated concentrations of the hormone cortisol, in addition to the increased rate of catabolism, play a negative role in nitrogen balance. Cortisol is a relevant component in protein metabolism, stimulating the uptake of amino acids by the muscle and exerting antihypertrophic effects.

Resistance training

Old are the positive effects of physical activity on human health. These benefits are acquired by several people who perform different types of exercises. In search of some of these benefits from health and aesthetic concern, interventions are studied such as resistance exercises that treat to increase muscle mass, known as muscle hypertrophy. Resistance exercise can be defined as any activity that requires a muscle to work against a strength, using the following force, which results in an increase in muscle strength, tone, mass, and muscle endurance. In fact, the muscle becomes larger and stronger in response to a systematized and specific training program, referring to this process as muscle hypertrophy. The muscle adapts in its thickness by increasing the size of the muscle fibers or via the increase of the amount of myofibrils, glycogen, and water parts stored within the muscles. In order to gain entry, protein synthesis to accommodate increased bench, reserve energy, remember that muscle glycogen is the main store of energy during physical activity.

Physical activity contributes to improving the quality of life of individuals. Resistance exercises should be highlighted. This type of activity promotes an increase in muscle mass called muscle hypertrophy. Molecular research that seeks to understand the cellular response to mechanical stress is called Mechanobiology. Mechanobiology is a young field and provides important information on cellular behavior during physical exercise. Knowing that hypertrophy has multiple benefits and meets a constant interest of general practitioners and sports professionals, as well as professionals working in the aesthetic treatment of some muscles of the body, we highlight the importance of investigating molecular mechanisms in which such cellular responses can be stimulated with the least effort on the part of the practitioner. This work discusses some implications that we can extract from Mechanobiology and hypertrophy concerning cellular responses, signaling pathways involved, anabolic diet, and its implications on protein synthesis.


If we eat too much protein in one meal, we have high levels of amino acids and, therefore, high levels of protein synthesis. However, as soon as the level of amino acids decreases, the level of protein synthesis also decreases quickly after the meal. Therefore, dividing protein replenishment is more advantageous. Regarding sport, food consumption may be of crucial importance for muscle growth. When we do weight training, we break down muscle proteins, and as we saw at the beginning, the muscle grows because it recovers from the trauma it has suffered. To form new proteins, we need amino acids to exert an osmotic pressure to attract proteins at the level in which the muscle protein has been lost. The blood carries these nutrients up to the muscles, thus allowing a repair.

As previously mentioned, the regulation of muscle growth can occur by protein synthesis or protein breakdown. Other than physical activity, nutrition is the other main factor that induces this adaptation. Spreading food consumption throughout the day causes muscle hypertrophy. This is important because when we digest, we have a kind of "spike" of hormone release. Insulin is one of those hormones released during digestion in response to food consumption. Amino acids that are taken through food can also induce insulin secretion, and protein synthesis also happens when amino acid plasma levels rise. You should consume the right amount of macronutrients (proteins, carbohydrates, and fats) and micronutrients (vitamins and minerals).

Hormonal factors

Studies have shown that local muscle contractions can increase the hypertrophy of distant muscles. Therefore, as these cells circulate through the bloodstream in any region of the body that has muscle damage, these substances trigger hypertrophic stimuli in these muscles. At the time of local lesion, the recovery is local, so fast that nothing happened. These substances are released through other processes, such as digestion of food one hour after the training, and may act in the recovery of local injuries resulting from D.O.M.S. without the need for large muscle lesions or hypertrophy throughout the body from the strength. Likely forms that do not increase hypertrophic muscle response remain unknown players.

Myostatin is a specific protein from muscle cells, and its job is to promote the aforementioned atrophy mechanism. If low levels of myostatin lead to more muscle mass, then there are genetic factors that, if present in less than 1% of the population, contribute to this. Since the muscle is the organ that burns calories just to exist, the more muscle, the more calories are spent on restoring your tissues. Nonetheless, the muscle by itself burns a discrete amount of calories. When you get a punch to the gut after making a bad joke that offended someone, you know the next day how it is a strong stimulus to the growth of abdominal muscle. If you do not know, let alone the physiologists do not know, I will do my best to explain the concept. Substances let out by tissue injury at the punch region enter the circulation. Those substances increase the secretion of other substances that act on the bone marrow and give rise to cells that can be stored in the muscles among other tissues.

Unlike body fat, you cannot avoid approaching a certain physique, thus muscle, mostly because of the importance of muscle to keep ourselves healthy. A pointed evidence of that is the decrease in muscle mass that happens after 25 years of age. The muscle is formed by multinucleated cells, called myofibers, coming from the fusion of several cells, called myoblasts. A sufficiently activated myoblast, called a satellite cell, will divide itself and the resulting myoblasts will fuse themselves to the myofibril, becoming one of its sources. However, there are other sources of myofibers, like some cells of our bone marrow.

Mechanisms of muscle hypertrophy

Increasing extracellular protein concentration at the cellular level can lead to cellular swelling stimulating the MAPK/ERK1/2 pathway which can stimulate protein synthesis. Over time with training, the muscle’s ability to withstand damage as a result of mechanical loading is also increased, however, this interaction may be specific to the strain and length of the muscle. Genetic variation in these traits appears to influence how we individually respond to physical activity and thus the training response. This molecular action appears to be time dependent, because increased IGF-1 levels occur four days after the increase in mTOR and p70S6K activities in rat muscle. Muscle IGF levels may be related to some contractile aspects of muscle adaptations to resistance training. Finally, in athletes with RT experience, the suppression of the IGF path was related to the reduced response of type II fetal myosin heavy chain.

Mechanisms of muscle hypertrophy - With mechanical overload, myofibrils are the initial targets where new sarcomere number increases (or decreases if immobilization or loss of muscle mass occurs) and myofibrils grow as a result of the addition of new myosin and actin. Proteins in muscle that are involved in the regulation of muscle growth are thought to determine the muscle’s maximum growth potential and influence individual variability in muscle growth in response to exercise. With resistance training, it is typically the number 1 and 2 muscle fibers (type 2x or 2b) that are recruited. Mechanotransduction has been the catch cry used to describe the molecular signal for growth and repair in response to contraction-induced muscle injury caused by physical activity. It refers to the way cells convert mechanical loading into cellular responses. Two of the more recent key factors identified as important in this process are the stimulation of amino acid sensing, particularly from leucine triggered by the rise in contractile activity and the insulin-like growth factor pathway.

Mechanical tension

The mechanical tension applied to the muscles does not only produce adaptations of the contractile apparatus but also results in a number of complex molecular changes. These molecular changes are implicated in alterations in the balance between protein synthesis and degradation, population of muscle stem cells, reduction of inflammatory response, angiogenesis, and even changes in mitochondrial function. Such changes accompany protein retention, favoring increases in muscle function, strength, power, and hypertrophy. This is why mechanical tension has long been considered the main factor responsible for muscle hypertrophy. Different models of muscle growth, such as in vitro tension models, agree that mechanical stress is necessary and sufficient to promote an increase in the diameter of the myofibers.

During strength training, the stress applied to the muscle promotes long-term changes known as hypertrophic adaptations that increase the microarchitecture of muscle fibers. This is made up of the realignment of the sarcoplasmic reticulum and the T-tubules, as well as hypertrophy of other structures within the muscle, such as the sarcoplasmic reticulum itself, mitochondria, glycogen, and creatine phosphate deposits. The myofibers adapt extensively to make use of the force generated by myosin.

Understanding muscle hypertrophy seems to be as easy as chewing when we aim to do so from a mechanical perspective. However, we must suck before biting directly with hypertrophy. That is due to hypertrophy being a multifactorial phenomenon resulting from a large body of interactions between mechanical, dietary, and even genetic factors. Nevertheless, due to the shortage of mechanical stress, the study consists mainly of muscle strength training and an increase in muscle mass.

Metabolic stress

When muscles are in a state of hypoxia, phosphorylated signaling molecules such as AMPK are activated, while p70-S6K is inhibited, which can block the protein synthesis induced by resistance training. Short periods of hypoxia during the recovery period between resistance training sets could potentially be beneficial to muscle adaptations. Some studies have shown that muscle hypertrophy from low-load resistance exercise can be similar to and, under specific conditions, greater than heavy resistance exercise. Blood metabolite concentration and changes in RPE may be used as potential indirect methods to monitor mechanical and metabolic stress caused by exercise, and the results of monitoring metabolite concentrations during the training session can determine fiber type activation, which is related to muscle strength and muscle hypertrophy.

Energy metabolism is a topic of interest in relation to muscle hypertrophy. Anaerobic exercise, using the stored energy of phosphocreatine and muscular glycogen, can lead to lactate production, causing acidosis in muscle fibers. Exercise with moderate and high repetitions can increase PGC-1α and VEGF expression, promoting capillary content and capillary growth in skeletal muscle. The capillaries in the skeletal muscle increase, improving microvascular perfusion and optimizing muscle force production. Metabolic stress is a consequence of energy insufficiency. Reduced mitochondrial function can lead to an increase in cytosolic calcium, which can activate mTOR through type I kinase such as calmodulin/calmodulin activate kinase and (the most common) type II kinase (the mTOR component of the mTOR complex 1)/1-phosphatidylinositol kinase/protein kinase B.

Muscle damage

The multiple muscle damaging ECC muscle actions that were performed with increasing angular velocities directly translated into an improvement in ECC muscle strength. There is an increase in the probability of recruitment of high-threshold motor units and augmentation of agonist and antagonist co-activation following an intermittent-maximal ECC leg-press exercise regimen, facilitating neuromuscular activation capabilities. Additionally, high or very high-force ECC muscle actions with a repeated bout effect preserve/increase muscle contractile function post-exercise, enhancing muscle strength. Nonetheless, speed could influence the exercise-induced muscle damage and the protective mechanisms that are elicited in the repeated bout effect. Furthermore, performing ECC muscle actions with a speed at which the peak torque is generated with a small joint range of motion is not recommended, as it may damage non-contractile structures of the muscle, connective tissue, and the contractile machinery.

One factor that can contribute to mechanical tension is skeletal muscle damage resulting in a still poorly understood muscle adaptive response that favors accretion of muscle mass. Damage to the contractile elements of skeletal muscle can result from both single and repetitive, unaccustomed lengthening muscle actions, such as those performed during eccentric (ECC) muscle actions. The repeated exposure to muscle damaging ECC muscle actions performed on an isokinetic dynamometer can enhance ECC muscle action strength, threshold for eccentric and associated concentric muscle actions, familiarization effects, joint proprioception, muscle, tendon and connective tissue mechanical properties, torque at increased velocities joint range of motion, angular displacement and maximum voluntary contraction and voluntary activation. This highlights the importance of familiarization for the outcomes of ECC muscle actions of a certain intensity and frequency for induction of muscle damage. Our group's preferred method of ECC muscle actions is the bilateral leg press or other two-limbed ECC actions performed in a closed kinetic chain. We have previously demonstrated that a 6-week high-intensity resistance-type exercise regimen that included maximal ECC unilateral knee extensor muscle actions on an isokinetic dynamometer resulted in a significant elevation in muscle soreness and creatine kinase activity, providing evidence of muscle damage.

Training strategies for muscle hypertrophy

The occurrence of muscle hypertrophy involves several factors; it is not a simple response. In general, the adaptations involve the mechanical work performed by the muscles during exercises, diet, and the energy balance between food intake and energy expenditure. The neuroendocrine benefits of resistance training can be affected by many exercise variables such as the number of sets, repetitions, muscle actions, variation of the order of the exercises, rest between sets, or the number of sets per muscle group performed per resistance training or per week. Research in this area has shown considerable heterogeneity in the effects of different sets performed per week on untrained and trained individuals in local muscle endurance, time to fatigue, strength, muscle hypertrophy, and body composition change, including an increase of lean mass and a decrease of fat mass. Data in the literature report that training split systems for strength and hypertrophy have effects in both untrained and trained subjects.

"Got muscle?" is a question rarely asked by women to one another - not due to lack of interest, of course, but rather because, according to researchers Garrett and Williams, hypertrophied muscles (i.e., "big guns") are mainly a male thing. In reality, muscle hypertrophy seems to be related to volume, intensity, rest, diet, time between sets and days of the week the exercise is practiced. The effects of using repetitions to muscle failure, two sets for upper limbs and ten sets for the lower limb, are widely discussed. Our understanding indicates that there is no difference in terms of recovery and in increasing strength levels or muscle hypertrophy after a 4-week resistance training intervention were reported in young women when comparing muscle failure with repetition zone [15]. The most commonly used repetition zones are 6-10. This way of working is safe, effective, allows for better concentration on the movement, longer isolation, better control of the muscle contraction, and better physical and mental adaptation to the effort requested.

Progressive overload

Progression does not always mean that weight should increase. The biological systems are trained to improve with increased work. Increasing the weight is just one of many ways to increase the work. You may not be able to increase the weight used in an exercise (sticking point), but the same weight can be used for the same number of repetitions but in a shorter period of time (either by decreasing the rest between sets or finding a faster cadence). Time under tension (slow eccentrics or pauses) or changing the range of motion of the exercise can also increase the work. You might even find that changing the workout itself (different but "equally" challenging exercises) can improve the strength of the first exercise. The biological systems respond to a challenge, and the result is a change. If the systems have performed at a higher rate, the body thinks this change is necessary.

Muscle hypertrophy (growth) is the main focus for the vast majority of people who engage in resistance training and is a common motivation for joining a gym. However, many people lack a thorough understanding of what factors are important to maximize our chances of increasing our body composition (people's bodies are made up of a percentage of muscle mass, body fat, and other tissues). Progressive overload is a term frequently used in the fitness world to describe "adding weights" to the exercises. This simple piece of advice has helped transform many looks, but if not understood correctly, it can prevent people from realizing their potential. It has helped create a culture of men in the gym that only half-rep squats 3 times their body weight and women scared to step into the weights section. The result is that hypertrophy is not maximized, and other important aspects of resistance training (bone and tendon health and maturity, improved movement, and metabolic efficiency) are overlooked. We all should have a thorough approach to our current and future biopsychosocial health.

Volume and intensity

Moreover, as in the example we took about muscle hypertrophy having some sort of bimodal distribution of reps, there might also be an aspect of hypertrophy being very specific to the individual. What is overreaching for you might be underreaching for me or in the middle, and then individual variation in need of overload has led to the reps economies we have shown earlier. For some people, hypertrophy does not require onerous weights nor does it require large amounts of exercise. They often stop early, and why this happens is an interesting topic of study. Of course, genetics play a role in the characteristics of muscles integrated in their function and all fundamental processes of growth.

Your muscle fibers adapt to either the volume of work you subject them to or the intensity at which you work these fibers. It seems like muscles need a certain time-under-tension to stimulate muscle hypertrophy, and this would be the total work you make if you keep the intensity stable. There is a relation to volume as well, as the more sets you do, the better the growth. However, what you also need to take into account is when exactly the hypertrophy happens. For example, a biceps curl has some parts of the movement that produce more growth than others. You could add these into isolation work, you could add ranges of motion where they happen, as well as reps that trigger this hypertrophy.

Exercise selection and technique

The perfect technique, both for performing basic exercises and for isolated ones, is highly variable from one individual to another. This is partly because each bodybuilder must try different techniques to find their own, personal and individual technique. If you do not try, you will not find it! But above all, it is because in nearly all cases it is impossible for a bodybuilder to realize that the technique they use when performing any given basic or isolated exercise is incorrect unless they perform the exercises under the supervision of an experienced coach, or in front of the mirror or video.

The hypertrophy of a given muscle, or group of muscles, is the product of optimal muscle tension, which in turn is the result of using the proper techniques when performing resistance exercises. Moreover, hypertrophy will be greater according to the greater number of motor units participating in, and the tension developing. Stimulation will, therefore, be greater in exercises such as squats where the quadriceps and gluteals work together, than in those that only involve one of them, such as leg extensions or leg curls. Good hypertrophy training involves selecting the exercises that activate more muscles or the largest part of them, that is, basic or multi-joint ones, and discarding the isolated or mono-articular exercises that some traditional bodybuilders are so fond of.