The Importance of Dietary Protein and Exercise for Skeletal Muscle Health

Occupying ~45–55% of total body mass in healthy adults,¹ skeletal muscle (SKM) is the only organ of the human body that we can directly influence—to some extent—what happens to it. We can care for it by exercising and eating a balanced protein-rich diet, or we can let it deteriorate by adopting a sedentary lifestyle and consuming processed foods with negligible nutritional quality.

The maintenance of SKM mass, function and quality is fundamental in dictating healthy aging and aiding recovery following periods of inactivity/disuse, whereas maximizing muscle mass (i.e., hypertrophy) is a common goal for athletes and exercise enthusiasts.

But how do we maintain this vital organ? What promotes SKM growth and how can we maximize it to support our health?

Regulation of SKM mass

SKM is regulated by the dynamic relationship between muscle protein synthesis (MPS) and muscle protein breakdown (MPB), which is ultimately driven by dietary protein feeding and exercise.

In the fasted (postabsorptive) state, MPB exceeds MPS, whereas in the fed (postprandial) state, MPS exceeds MPB; thus, net protein balance is achieved across daily feeding cycles.

The building (i.e., anabolic) effects of protein feeding are driven by the delivery and incorporation of amino acids (AA) from dietary protein sources into SKM proteins. Importantly, the essential amino acids (EAA) – rather than non-essentials – drive these increases in MPS following a protein feed.^2,3

“EAAs are the driving force behind increases in MPS,” said Dr. James McKendry, assistant professor in nutrition and healthy aging at The University of British Columbia, Canada. “Protein sources with a greater EAA content are, generally, more effective at stimulating MPS, which occurs in a dose-response manner – the more EAAs, the greater the MPS response (until MPS is saturated).”

Compared to feeding alone, exercise (especially resistance exercise) accentuates the MPS response by making SKM more receptive to EAA.

“The muscle anabolic actions of dietary protein and exercise are synergistic, with exercise enhancing the utilization of dietary protein-derived amino acids for muscle protein synthesis,” explained Dr. Leigh Breen, professor in translational muscle physiology at the University of Birmingham, UK.

“These combined stimuli of exercise and dietary protein intake lead to a positive net muscle protein balance (where rates of synthesis chronically exceed rates of breakdown) that, when repeated frequently over time, provides the basis of muscle protein accretion or hypertrophy,” he continued.

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Conversely, sedentarism and aging impair the MPS and MPB response, often leading to muscle atrophy. “Inactivity leads to the desensitization of skeletal muscle to dietary amino acids. The removal of contractile activity is such a robust stimulus that, in many cases, simply consuming more or better-quality protein cannot overcome the blunted anabolic response,” said McKendry.

The acute effects of protein feeding

Following oral protein feeding, an initial lag of ~45–60 minutes occurs before MPS increases due to esophageal transit, digestion and absorption, arrival at the target tissue (i.e., SKM) and activation of signaling pathways. MPS then increases two- to three-fold, peaking between one and a half to two hours post-feed before returning to baseline.

Despite continued plasma EAA availability, MPS plateaus and begins to decline—a phenomenon known as “muscle full.” ⁴ Therefore, a refractory period must exist before further MPS stimulation is achieved.

“The muscle full effect describes a plateau in SKM protein synthesis, and even in the presence of additional AAs, the muscle can no longer continue increasing protein synthesis – the muscle is full!” McKendry explained.

“In practical terms, this suggests that spreading protein intake across multiple meals throughout the day might be more effective for maximizing muscle protein synthesis than consuming a large amount of protein in one sitting. This approach ensures that the muscle is consistently receiving the necessary AAs to support MPS without hitting the ‘muscle full’ threshold,” said Breen.

Importantly, the muscle full state is unable to be overcome by additional nutrient signals/substrates regulating MPS and pharmacological or nutritional interventions commonly utilized to enhance nutritive blood flow.^5,6 Nonetheless, resistance exercise can delay muscle full onset due to the increased anabolic sensitivity of SKM to dietary AA. However, aging and physical inactivity results in a premature onset due to association with desensitization to anabolic stimuli (i.e., exercise and nutrition).

“Exercise training, age and muscle disuse likely influence the threshold for the muscle full effect to the greatest extent,” said McKendry.

While MPS is stimulated, MPB is inhibited by ~50% in young muscle – although this is significantly blunted in older muscle – due to the reflex actions of insulin.⁷ Notably, insulin has an apparent permissive role in MPS when there is sufficient AA availability but plays a clear and primary role in aiding muscle anabolism through the suppression of MPB, regardless of AA availability.⁸

“During and following exercise, MPS increases, but so does MPB – the turnover of muscle proteins is elevated and the net protein balance remains slightly negative. However, when combined, exercise and dietary protein work in concert to substantially augment MPS while simultaneously reducing MPB,” McKendry explained.

As increases in MPS are far greater than increases in MPB, MPS is the driving force behind nutrient-induced muscle anabolism.

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Associated intracellular signaling with MPS

It has been well-established ^9,10 that the mammalian target of rapamycin (mTOR) is a key cell signaling pathway regulating nutrient and exercise-induced alterations in MPS and subsequent SKM hypertrophy.

Activation of the mTORC1 signaling pathways leads to a cascade of signals resulting in the activation of downstream regulators such as 4E-binding protein (4E-BP1), ribosomal protein s6 kinase (p70S6K1) and ribosomal protein s6 (RPS6). This ultimately leads to an upregulation of mRNA translation and, therefore, MPS.

Furthermore, leucine – an essential and branched chain AA – can independently activate mTORC1 and downstream signaling, leading to increased MPS.¹¹

“Leucine is critical for stimulating MPS; it triggers a cascade of signaling events, leading to an increased MPS response,” McKendry stated. “While the other EAAs are crucial in maintaining an elevated rate of MPS for hours after protein ingestion, without sufficient leucine present (2–3 g) in the protein to trigger MPS, it will likely remain at postabsorptive rates.”

Interestingly, the coordination of MPS and molecular signaling differs significantly between different forms of exercise (i.e., resistance vs endurance exercise). However, there is likely some crossover in these responses, which may depend on training status and exercise intensity.

“Resistance exercise primarily stimulates the synthesis of myofibrillar proteins (i.e., the contractile components of skeletal muscle), which are responsible for muscle growth and strength. On the other hand, endurance exercise primarily enhances the synthesis of mitochondrial proteins, which improve the muscle's oxidative capacity and endurance performance. The molecular signaling pathways stimulated by endurance exercise include AMPK and PGC-1α, key regulators of mitochondrial biogenesis and function,” Breen discussed.

What can we do to optimize SKM mass gains to support healthy aging?

Ideally, an active lifestyle supported by a healthy balanced diet high in protein should be adopted throughout an individual's life. This is even more important to consider as we get older due to the impact of sarcopenia – the age-related decline in muscle mass and function.¹²

Involuntary loss of SKM mass, strength and function is a fundamental cause and contributor to disability in older adults and even rates of mortality.¹³ From around the third decade of life, SKM mass and strength begin to decline at a rate of 3–8% per decade, with declines even higher after 60 years of age.¹⁴

Breen discussed several key components that should be considered for an optimal exercise regime to maximize MPS and SKM mass gains. Initially, individuals should “engage in regular resistance exercise training to stimulate muscle growth and to train the major muscle groups at least twice a week.” There should be a “mix of compound and isolated movements to ensure balanced muscle development.” To allow progression in training, “the intensity, volume or frequency of workouts should gradually increase to continually challenge the muscles and promote growth.”

“Adequate rest and recovery between workouts should occur to prevent overtraining and promote muscle repair. Further, sufficient protein should be consumed to support muscle repair and growth – aiming for at least 1.4–1.6 grams of protein per kilogram of body weight per day, spread across multiple meals,” he continued.

Perhaps one of the most important considerations is that SKM hypertrophy is a slow, gradual process. Maintaining a consistent resistance exercise training program is crucial to achieving long-term results that can contribute to maximizing healthy aging.