Muscle Gain

Muscle gain, or hypertrophy, refers to an increase in the cross-sectional area (size) of a muscle fiber or whole muscle, primarily as a result of an increase in the size or number of myofibrils (i.e., bundles of protein filaments that produce muscle contraction) within preexisting muscle fibers.^[1][2]

Muscle gain is commonly estimated using whole-body assessments of body composition, which differ in the number of compartments body mass is divided into. A 4-compartment (4C) model is considered the gold-standard and divides the body into total body water, bone mineral content, fat mass, and fat-free mass. However, it requires a variety of equipment and is costly and time-consuming, so it’s not commonly used. Other methods to evaluate body composition include the 3-compartment (3C) model, which divides the body into bone mineral content, fat mass, and fat-free mass (e.g., dual-energy x-ray absorptiometry — DXA), and the 2-compartment (2C) model, which divides the body into fat mass and fat-free mass (e.g., bioelectrical impedance analysis, skinfolds). To assess growth of specific muscle groups, assessment methods such as ultrasound, computed tomography, and magnetic resonance imaging are also used.^[3]

Resistance exercise is the most effective form for muscle gain. Research suggests that it should be performed with a range of 10–20 sets per muscle group per week,^[4][5] although some people may experience substantial muscle gain performing a lower number of sets per week. Each muscle group should be trained at least once per week.^[6] When performing more than 10 sets per week for a given muscle group, it may be beneficial to divide the sets over several days (e.g., 6 sets/day on 2 days, rather than 12 sets on one day).^[7]

Each set should be performed to, or close to, muscular failure (i.e., the point at which another concentric repetition cannot be performed with proper form),^[8] using a load equivalent to approximately a 5- to 30-repetition maximum.^[9] Machine and/or free weight exercises may be used, as they are equally effective.^[10] A rest interval of about 60–180 seconds should separate each set, with the upper end of this range generally reserved for multi-joint exercises (e.g., squats).^[7]

Supplements marketed to boost muscle gain are typically purported to accomplish this feat when combined with a resistance-exercise program. A supplement may support muscle gain by stimulating muscle protein synthesis, improving resistance exercise performance (via enhancing force production or muscular endurance), or supporting recovery (via attenuating muscle damage).

Creatine monohydrate is by far the most effective supplement to enhance muscle gain.^[11] Other popular options include caffeine, beta-alanine, ashwagandha, betaine, citrulline, HMB, alpha-GPC, taurine, branched-chain amino acids, and nitrate.

Positive energy balance (i.e., energy input greater than energy consumption) has been shown to induce muscle gain in the absence of resistance exercise,^[12][13] and combining a hypercaloric diet with resistance exercise enhances muscle gain.^[14][15] To maximize muscle gain, total daily protein intake should be between 1.6 and 2.2 grams of protein per kilogram of body weight (g/kg),^[16] ideally split between multiple meals containing 0.4–0.55 g/kg consumed 3–5 hours apart.^[17] A total daily carbohydrate intake of at least 3–5 g/kg is recommended,^[15] while dietary fat intake should fall between 20% and 35% of total energy intake, or about 0.5–1.5 g/kg/day.^[18]

How much muscle an individual gains in response to a resistance exercise program is influenced by their age, genetics, lifestyle factors (i.e., sleep, nutrition, and stress management), and training history.

The magnitude of muscle gain in response to resistance exercise appears to decrease with age^[19][20][21] and training experience (i.e., untrained individuals further from their genetic ceiling of muscle mass gain muscle faster than trained individuals).^[15] Twin and family studies have reported a high heritability of muscle size,^[22][23] and the presence of certain genes has been associated with greater muscle gain.^[24]

While an individual’s overall capacity to respond to resistance exercise is determined by their genetics, resistance exercise programs can be altered (e.g., increasing volume and/or frequency) to provide a novel, more robust stimulus to make the most of one’s muscle-building potential.^{[25] [26][27]}