Resistance training is the process of exercising with external resistance for the purpose of enhancing the functional performance of muscle, improving physical appearance or a combination of the two and is a primary reason why many individuals start a workout program. Resistance training can both improve strength and increase muscle size simultaneously; however, there is a distinct difference between training for maximum force output (strength) and muscle growth. Muscle growth from resistance training occurs by either increasing muscle fiber thickness or the volume of fluid in the sarcoplasm of muscle cells.

Resistance training alone does not induce muscle growth; the training load has to cause fatigue to stimulate the physiological mechanisms responsible for increasing muscle mass. The overload principle of exercise program design dictates that to stimulate physiological changes such as muscle growth, it is necessary to apply a physical stimulus at an intensity greater than the body is accustomed to receiving. 

Understanding how the muscular system adapts to the imposed demands of resistance training can help you determine the best way to train your clients for maximal muscle growth. Existing research offers guidance as to how the body may respond to a stimulus, but everyone will experience a slightly different physiological outcome to the imposed demands of resistance training. The ability to add mass and increase the level of lean muscle is based on a number of different variables including sex, age, resistance training experience, genetics, sleep, nutrition and hydration. Other emotional and physical stressors, each of which applies a stress that can change how an individual’s physiological systems adapt to resistance training, also influence one’s ability to add mass. For example, too much stress at work or a lack of sleep may significantly reduce the ability to grow muscle. Knowing how to apply this science, however, can greatly influence your ability to help your clients maximize their results.

Mechanical and Metabolic Stress

It is well known that physical adaptations to exercise, including muscle growth, depend on the application of the acute variables of program design. There is absolutely no question that resistance training causes muscle growth; however, the science is undecided on exactly what causes muscle growth, although current evidence points to mechanical tension as the primary stimulus.

Resistance training causes two specific types of stress—metabolic and mechanical—and both types can provide the necessary stimulus for muscle growth. Brad Schoenfeld, PhD, is a researcher who has performed exhaustive literature reviews on training for muscle growth. “Mechanical stress is unquestionably a primary driving stimulus in post-exercise muscle growth,” explains Dr. Schoenfeld. “There is compelling evidence that metabolic stress may also contribute to hypertrophic adaptations. A problem with the research is that mechanical and metabolic stress occur in tandem, making it difficult to tease out the effects of one from the other.”

More recent reviews reinforce the idea that mechanical tension is the primary driver of hypertrophy, with metabolic stress and muscle damage acting as secondary or supportive mechanisms rather than independent requirements for growth. These mechanisms are strongly influenced by training variables such as load, volume, range of motion and proximity to failure.

Mechanical stress refers to the physical stresses applied to the structures of the motor neuron and its attached muscle fibers, collectively referred to as a motor unit. Resistance training causes microtrauma to muscle tissue which, in turn, signals the biochemical reaction to produce new satellite cells responsible for repairing the mechanical structure of the muscle tissue as well as building new muscle proteins. Additionally in his research on cellular adaptations to resistance training, Spangenburg recognized that “mechanisms activated during mechanical loading of muscle signal changes which create hypertrophy.”

Metabolic stress occurs as the result of a muscle producing and consuming the energy required to fuel contractions. The moderate-intensity, high-volume training programs responsible for muscle growth use the glycolytic system of energy production. A byproduct of anaerobic glycolysis is an accumulation of lactic acid and hydrogen ions that changes blood acidity and creates acidosis. Evidence suggests a strong relationship between blood acidosis and elevated levels of growth hormone that support muscle protein synthesis. In their review of the research, Bubbico and Kravitz noted that, “Metabolic stress, a result of the byproducts of anaerobic metabolism (i.e., hydrogen ions, lactate and inorganic phosphate), is now also believed to promote hormonal factors leading to muscle hypertrophy.”

There are two specific types of hypertrophy (the technical term for muscle growth). Myofibrillar hypertrophy refers to the increase in size or thickness of individual actin and myosin protein filaments, which can improve the force production capacity of the myofibrils. Myofibrillar hypertrophy does not lead to larger muscles; rather, it results in thicker muscle fibers capable of generating more force. Sarcoplasmic hypertrophy is an increase in the volume of the semifluid interfibrillar substance in the intercellular space that surrounds an individual muscle fiber. This fluid contains the proteins used to promote tissue repair and growth. Sarcoplasmic hypertrophy can cause the cross-sectional area of muscle fibers to increase, but most of the enhanced muscle size is due to an additional volume of the sarcoplasm and non-contractile proteins not directly involved with force production. Resistance training with heavy loads to fatigue can result in a combination of sarcoplasmic and myofibrillar hypertrophy.

Designing exercise programs that build muscle mass requires knowing how to apply the stress of exercise in a way that doesn’t create negative interference with other stressors. Effective exercise professionals should know how to manage exercise stress in such a way to promote an optimal response from a workout program. Designing a resistance-training program with a proper application of variables—specifically the exercises, intensity, repetition ranges, sets and rest intervals—to create both a metabolic and mechanical demand on muscle tissue can stimulate the production of hormones and promote the synthesis of contractile proteins responsible for muscle growth. 

Mechanical Stimulus

Knowing how to design exercise programs to stimulate maximal muscle growth requires an understanding of muscle fiber physiology. A motor neuron receives an action signal from the central nervous system (CNS), activating the attached muscle fibers. There are two basic muscle-fiber classifications: type I (slow-twitch) and type II (fast-twitch). Type I muscle fibers are also known as aerobic muscle fibers due to their ability to create energy from oxygen, which allows them to produce force over an extended period of time. 

The two types of type II muscle fibers discussed most frequently in exercise physiology texts are types IIa and IIx (historically referred to as IIb in some literature). Type IIx fibers use stored adenosine triphosphate (ATP) to generate a high amount of force in a short period of time without the use of oxygen making them completely anaerobic. Type IIa fibers can take on characteristics of either type I or type IIx fibers, depending on the applied training stimulus. Contemporary resistance-training research consistently shows that hypertrophy can occur across both fiber types regardless of proximity-to-failure and the specific load used.

The initial improvements in strength from a resistance-training program are primarily due to improved neural function as external resistance creates a stimulus that increases both the number of motor units activated and their speed of contraction. One of the long-term adaptations of muscle to resistance training is an increase in muscle fiber cross-sectional area. As the cross-sectional area increases in size, the fibers have more surface tension and become capable of generating higher amounts of force. Muscles with a larger cross-sectional area of individual muscle fibers are capable of producing greater amounts of force. Despite a common misperception that lifting weights can lead to an immediate increase in muscle size, it can take eight weeks or longer, even in a well-designed program, for significant muscle growth to occur.

According to the all-or-none theory, a motor unit is either active or inactive; however, when a motor unit is stimulated to contract it activates all the muscle fibers connected to it. Slow-twitch motor units have a low threshold for activation and low conduction velocities, and are best suited for long-duration activity requiring minimal force output because they attach to type I muscle fibers. Fast-twitch motor units are attached to type II muscle fibers and have a higher activation threshold, are capable of conducting signals at higher velocities and are better suited to producing force rapidly because they can produce ATP quickly without the need for oxygen. Fast-twitch muscle fibers also have a greater diameter than type I fibers and play a more significant role in hypertrophy. Recruiting and innervating type II muscle fibers requires creating enough mechanical and metabolic overload to fatigue the involved muscle by the end of the set.

Metabolic Stimulus

Muscle motor units are recruited via the size principle with smaller, type I motor units recruited first before the larger type II fibers capable of generating the force necessary to move heavy loads. When type II muscle fibers are recruited, they use stored muscle glycogen to create the ATP required for contraction and this leads to an adaptation that can greatly influence muscle size. As muscle cells deplete glycogen for fuel, they will adapt by storing more glycogen during the recovery phase. One gram of glycogen will hold up to 3 grams of water when stored in muscle cells. Performing high repetitions to momentary fatigue can not only create the acidosis to stimulate growth hormone production, but can deplete stored muscle glycogen, resulting in an increase in muscle size once it is replenished.

Mechanical tension created by resistance training is widely considered the primary driver of hypertrophy. When muscles are challenged with sufficiently heavy or fatiguing loads, individual fibers experience disruption to their structural proteins, which in turn triggers local signaling pathways and an increase in muscle protein synthesis during recovery.

Endocrine Stimulus for Hypertrophy

The endocrine system produces the hormones that control cellular function. Mechanical and metabolic stress applied to muscle fibers are associated with activation of the endocrine system and can increase the production of the hormones responsible for repairing damaged muscle tissue and growing new protein cells. The hormones testosterone (T), growth hormone (GH) and insulin-like growth factor (IGF-1) are produced as a response to resistance training and play a permissive/supportive role in the protein synthesis responsible for repairing and growing new muscle. The rate of protein utilization and subsequent muscle growth is related to the damage of the muscle fibers involved in training. Moderate to heavy loads performed for higher repetition ranges can generate higher levels of mechanical force, which creates more damage to muscle protein and is often accompanied by increased production of T, GH and IGF-1 to remodel protein and build new muscle tissue.

More recent studies have challenged the idea that transient post-exercise increases in systemic hormones like T and GH are the key drivers of muscle growth. When training volume and effort are matched, hypertrophy appears to be largely independent of the magnitude of the acute hormonal response and instead is more closely related to local mechanical tension, recruitment of higher-threshold motor units and the total amount of hard work performed near failure. In practical terms, it is not necessary to “chase” a hormone spike; rather, it is more important to ensure that clients perform enough challenging sets for each muscle group across the week.

The endocrine system experiences acute and chronic adaptations to resistance training, but these should be viewed as one part of a larger adaptive picture rather than the primary cause of hypertrophy. In the acute phase immediately post-exercise, the endocrine system will produce T, GH and IGF-1 to promote repair of the damaged tissue. The long-term endocrine system adaptation is an increase in the receptor sites and binding proteins, which allow T, GH and IGF-1 to be used effectively for tissue repair and muscle growth. Schoenfeld observed that muscle damage as a result of mechanical tension and metabolic stress from high-intensity exercise is an effective stimulus for producing the hormones responsible for cellular repair and that IGF-1 is “probably” the most important hormone for enhancing muscle growth. Whether the endocrine system is influenced more by mechanical or metabolic stress is not certain; however, research indicates that organizing the volume and intensity of a training session to feature heavier loads with shorter rest periods can lead to an increase in the production of anabolic hormones that promote muscle growth, even though these acute hormonal changes alone do not guarantee greater gains if overall workload and proximity to failure are not sufficient.

Resistance Training for Muscle Growth

When the goal is hypertrophy, the primary variables to manipulate are load, effort, volume and rest intervals. For many years, a narrow “hypertrophy zone” of moderate loads and 8–12 repetitions per set was promoted as the best way to build muscle. More recent research, however, demonstrates that muscle growth can occur across a much wider range of loads—as low as ~30–50% of one-repetition maximum (1-RM) and as high as ≥70–80% of 1-RM—provided that sets are taken close to volitional fatigue and weekly training volume is sufficient. This means that health and exercise professionals can select from a variety of rep and load schemes and prioritize what a client can perform safely and consistently, rather than trying to stay within a single “magic” rep range.

In practical terms, this opens the door to lighter-load, higher-repetition work (e.g., 12–20+ reps) for deconditioned clients, those with joint issues or limited equipment, and heavier-load, lower-repetition work (e.g., 4–6 reps) for clients who also want to emphasize strength—so long as the working sets are challenging and performed near fatigue. Moderate loads in the traditional 6–12-rep range remain a useful “middle ground” for many clients because they allow relatively heavy weights to be used without excessive joint stress and make it easier to accumulate the total number of hard sets per muscle group needed for muscle growth.

It is simply not enough to lift a weight for a high number of repetitions if it does not cause momentary muscle fatigue. The body is extremely efficient at conserving and utilizing energy, so if the same exercise is repeatedly performed with the same load, then it could limit the amount of mechanical or metabolic stress placed on the muscle and minimize the training effect. To stimulate muscle growth, the variables of exercise program design must be applied in a manner that places a mechanical stress on the muscle tissue and also creates a sizable metabolic demand. Zatsiorsky and Kraemer identified three specific types of resistance training: the Maximal Effort Method, the Dynamic Effort Method and the Repeated Effort Method (Table 1).

Maximal Effort Method

The Maximal Effort (ME) Method of strength training uses heavy loads to enhance motor unit activity by innervating the higher threshold type-II motor units and their attached muscle fibers. ME training can improve both intramuscular coordination, which is the number of motor units functioning within a specific muscle, along with intermuscular coordination, which is the ability of a number of different muscles to time their firing rates to contract simultaneously. The primary stimulus of ME training is mechanical: specifically, myofibrillar hypertrophy, which can greatly increase the force output of a muscle without adding too much size. The ME method is effective for strength development but is not the most effective approach for increasing muscle size.

The Dynamic Effort Method

The Dynamic Effort (DE) Method of strength training uses non-maximal loads moved at the highest attainable velocity to stimulate the muscle motor unit. The DE Method activates the contractile element of muscle to create an isometric contraction and place tension on the body-wide network of fascia and elastic connective tissue. When the contractile element shortens, it loads the fascia with elastic mechanical energy that, when rapidly shortened, creates an explosive action to move an external load. The DE Method is the most effective means of increasing the rate of force development and developing explosive power required for many sports or dynamic activities. However, training with the DE Method does not place a significant amount of either mechanical or metabolic stress on the contractile element of muscle, which are necessary for stimulating muscle growth.

The Repeated Effort Method

The Repeated Effort (RE) Method of strength training requires the use of a non-maximal load performed until momentary muscle failure (the inability to perform another repetition). By performing the final few repetitions per set in a fatigued state to stimulate all of the motor units, the RE Method can engage all the fibers in an involved muscle and create a significant overload. Due to high repetition ranges performed with a moderately heavy load, the RE method stimulates hypertrophy by creating both a mechanical and a metabolic overload and is frequently used by bodybuilders for increasing lean muscle mass. The RE Method utilizes slower motor units for the initial repetitions; as these motor units begin to fatigue, the muscle will recruit type II high-threshold motor units to sustain the necessary force production. Once the high-threshold motor units are activated, they fatigue quickly, leading to the end of the set. As anaerobic type II fibers are used, they create energy through anaerobic glycolysis, which produces metabolic waste like hydrogen ions and lactic acid that change blood acidity. Research suggests that acidosis—the change in blood acidity due to an accumulation of blood lactate—is associated with an increase in GH and IGF-1 to promote tissue repair during the recovery phase.

It is important to note that if the load is not sufficient or the set is not performed to failure, then it will not stimulate the type II motor units or create the requisite metabolic demand that help promote muscle growth. More recent meta-analyses suggest that sets taken very close to failure—with approximately one to three repetitions of volitional failure—can stimulate similar hypertrophy to true failure while potentially reducing accumulated fatigue and allowing more total productive volume across the week. For many clients, especially beginners, older adults or those with higher overall life stress, coaching “high effort” rather than mandatory failure on every set may be a safer and more sustainable application of the RE Method.

Briefly, the RE Method provides three key advantages:

1. It has a greater impact on the metabolic function of the muscle, provoking greater levels of hypertrophy.
2. It involves a significant number of motor units, leading to strength gains.
3. It can have a lower risk of injury when compared to the ME Method of training.

 Table 1: Classifications of Strength Training

*To fatigue is within 0–3 reps of task failure based on client’s ability and goals

Source: Adapted from Zatsiorsky and Kraemer, 2006.

Rest and Recovery

Often the most overlooked variable of any exercise program is the post-workout recovery period. Whether it is mechanical or metabolic stress that provides the stimulus for muscle growth is not as important as allowing the time for T, GH and IGF-1 to promote muscle protein synthesis after a training session. Exercise is a physical stimulus applied to a muscle and is only part of the equation responsible for muscle growth. Adequate recovery is essential to allow the trained muscles sufficient time to replace muscle glycogen and the physiological process to repair and rebuild new tissue. The most active period of protein synthesis is the 12 to 24 hours after a hard training session. The frequency of training a muscle group is dependent upon the individual’s training goals, experience and conditioning status. Appropriate recovery for muscle growth is approximately 48 to 72 hours before exercising the same muscle group.

Inducing metabolic and mechanical stress in the gym will only go so far in promoting muscle growth. T and GH are produced during the rapid eye movement (REM) cycles of sleep, meaning that after strength training a full night’s rest is critical for promoting muscle growth. Insufficient rest and recovery do not allow for optimal muscle protein synthesis and could lead to an accumulation of energy-producing hormones like epinephrine and cortisol, which can reduce the ability to generate new muscle tissue. Loss of sleep, loss of appetite, lingering illness and cessation of gains from exercise are all symptoms of overtraining, which can significantly affect an individual’s ability to achieve their fitness goals. “Under-recovered” is another way to think of overtraining. “Promoting muscle growth requires periods of off-loading (active rest) to allow for a complete recovery,” says Dr. Schoenfeld. When working with clients to promote muscle growth, encourage them to allow proper time for sleep to ensure optimal results.

Developing a Workout Program for Muscle Growth

When designing a hypertrophy-focused program, the goal is to prescribe enough hard sets per muscle group, with an appropriate load, effort, tempo and rest interval, so that the target muscles are challenged close to fatigue while still recovering between sessions. For most clients, working sets in a variety of rep ranges (e.g., 6–12, 8–15, or even 12–20+) can be effective, as long as they are taken to within roughly 0–3 reps of volitional failure. Short- to moderate-duration rest intervals of about 60–90 seconds for most assistance and isolation work can help maintain a higher metabolic demand, while slightly longer rests (90–180 seconds) may be appropriate for heavy compound lifts to preserve performance on subsequent sets. Completing approximately three to four challenging sets per exercise using at least 30% 1-RM is a practical way to accumulate enough volume per muscle group over the week to promote hypertrophy.

The tempo of movement should be relatively controlled during both phases of the lift. A one- to two-second concentric phase and a slightly slower two- to four-second eccentric phase can help maintain tension on the target muscles and may enhance mechanical strain and mind–muscle connection. From a hypertrophy standpoint, eccentric actions appear to play an important supportive role in muscle development; lengthening exercise is associated with robust increases in muscle protein synthesis and structural remodeling of the tissue.

Compound, multijoint movements with free weights like barbells, dumbbells and kettlebells involve a number of different muscles and can generate a sizable mechanical and metabolic effect during training, especially in moderate to higher repetition ranges. Selectorized machines that focus on muscle-isolation or single-joint movements allow mechanical stress to be placed directly into localized tissue with greater stability and often less joint stress. Dr. Schoenfeld has acknowledged that each plays a role in optimal muscle growth: Free weights involve a number of contributing muscles—which can improve overall muscle density and coordination—while the stabilization provided by machines allows for heavier loads or higher levels of fatigue on specific muscles without overtaxing the stabilizers.

The following exercise program is based on current research related to achieving muscle growth and is intended for clients with at least one year of consistent resistance training experience. The combined mechanical and metabolic demand from this type of higher-volume training can create noticeable muscle soreness, so exercise professionals should monitor recovery and adjust volume or load as needed. Each session should begin with a complete dynamic warm-up featuring a variety of body-weight movements and core exercises to ensure that the tissues are prepared to handle the stresses of the workout. Even if a training session focuses on one or two primary body regions, performing a warm-up for the entire body can help increase caloric expenditure, reinforce fundamental movement patterns and promote circulation for muscles trained earlier in the week.

The resistance-training program should start with compound movements using free weights to engage as much muscle as possible and, over the course of the training session, gradually transition toward using machines or more isolated movements to place targeted stress on specific muscles when fatigue is higher.

The final exercise of each workout is performed on a machine to allow for a drop set when appropriate. A drop set involves using a given weight for as many repetitions as can be performed with good technique and then, when fatigue occurs, lowering the amount of weight and continuing for additional repetitions. Drop sets can induce significant metabolic and mechanical stress but can also create extreme discomfort and add to overall fatigue. For that reason, they are best reserved for the last exercise of a workout and used sparingly based on the client’s training age, goals and recovery capacity.

Each client will require a program specific to their needs, schedule and tolerance for training volume, but the following four-day template illustrates one approach to prioritizing muscle growth while still leaving room for low-intensity cardio and active recovery. This program features relatively limited moderate- to high-intensity cardio because aggressive energy expenditure can, in some cases, interfere with strength and hypertrophy gains if total training stress and recovery are not well managed. Low- to moderate-intensity cardiorespiratory exercise on non-lifting days can still be included to support cardiometabolic health and overall energy expenditure, provided it does not compromise recovery from resistance training.

Day 1: Lower Body

 *To fatigue (within approximately 0-3 reps of task failure, based on client ability and goals)

Day 2: Upper-Body Pull

 *To fatigue (within approximately 0-3 reps of task failure)

 Day 3: Upper-Body Push

*To fatigue (within approximately 0-3 reps of task failure)

Day 4: Rest or Low-Intensity Cardiorespiratory Exercise

Conclusion

The science behind muscle growth helps explain what generations of lifters have discovered through experience: Muscles grow when they are challenged with progressively heavier and more demanding work, and when they are given enough time and resources to recover. Mechanical tension appears to be the primary driver of hypertrophy, with metabolic stress and muscle damage playing important supporting roles. In practice, this means helping clients perform enough hard sets each week, using loads and exercises that they can execute safely and consistently.

Some clients will gravitate toward higher-rep, metabolically demanding work, while others may prefer heavier loads for fewer repetitions to emphasize mechanical stress. Both approaches can be effective as long as total volume, proximity to failure and recovery are managed appropriately. Your role is to match the method to the person in front of you—considering their goals, training age, lifestyle stress and willingness to tolerate discomfort. Adding lean muscle mass does require effort and a tolerance for some “good discomfort,” but it should never mean ignoring pain or sacrificing long-term joint health. When you anchor your programs in sound science and coach clients to train hard, recover well and progress gradually, “no guesswork, more muscle” becomes a realistic, sustainable outcome.