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The Practical Scientist – Part II
by: Jamie Hale

It is a well known fact that a proper resistance training program stimulates muscle protein synthesis. How does various nutrients and hormones combined with exercise affect net muscle protein balance? In this installment of The Practical Scientist we will look at Human Muscle Protein Synthesis After Physical Activity and Feeding by Benjamin F. Miller to answer some of these questions. This paper will help readers make wise choices regarding nutrition and take advantage of the anabolic stimuli caused by resistance training.

Key points from Human Muscle Protein Synthesis After Physical Activity and Feeding. Benjamin F. Miller.

The increase in protein synthesis after feeding is a systemic transient storage phenomenon, whereas physical exercise stimulates a local long term adaptive response. Providing nutrition after physical activity takes advantage of the anabolic signaling pathways that the physical activity has initiated by providing amino acid building blocks and energy for protein synthesis.

Physical activity has triggered an adaptive response to which the nutrition provides the necessary building blocks for an optimal response (my comment: No matter what you tell some trainees they can’t seen to get it through their head that training alone is not sufficient to optimize gains in skeletal muscle tissue.) In other words, nutrition is necessary to take advantage of an adaptive environment created by exercise.

Just as adipose is the storage depot of excess free fatty acids and muscle and liver glycogen are the storage site of glucose (my comment: kidney contains small amounts of glycogen), skeletal muscle can be viewed as the storage depot of amino acids. As mentioned by Wolfe, skeletal muscle protein is the only AA reserve in the body capable of significant losses without compromising the ability to sustain life. In the fasted state, skeletal muscle protein breakdown increases to sustain the free AA pool (my comment: excerpt from Protein Essentials by Jamie Hale- The free amino acids are located mainly in the cytosol (aqueous part of cytoplasm) and circulating blood. To keep the pool adequately supplied, it is important to consume a sufficient quantity of indispensable amino acids daily. Amino acids released by the breakdown of dietary or tissue protein, synthesized de novo, or mixed with other free amino acids distributed throughout the body make up the amino acid pool. The pool provides amino acids for protein synthesis and oxidation and contains about 100 grams of amino acids. It is small in comparison with the amount of total protein stored in the body (about 12 kg in a 70 kg man). The free pool is approximately 1 percent of the size of the amino acids stored in tissue. The free pool of amino acids is important for protein metabolism for various reasons. It provides a link between dietary and body protein, as they both contribute to it. The free pool is also involved with protein turnover. It has also been noted that concentrations of certain amino acids in the pool, particularly glutamine, are directly correlated with muscle protein synthesis. Approximately 60 percent of the amino acid pool is compromised by glutamine). Conversely, when fed, AA stimulate muscle protein synthesis to maintain AA stores during subsequent fasts.

A flooding dose of essential amino acids stimulated the fractional synthesis rates of skeletal muscle protein when simultaneously measured by the continuous infusion technique. However, when nonessential AA were used as a flood, FSR was not increased (my comment: the body makes a sufficient quantity of nonessential amino acids to support needs from metabolic intermediates and other amino acids, including more in the diet does not further enhance MPS). The stimulation of muscle protein synthesis by EAA is an interesting display of human design. Because EAA by definition can only come from the diet, the increased concentration of EAA indicates that a meal has been consumed. The signaling of a consumed meal would not work with NEAA because the concentrations of NEAA can change in the absence of a meal through transamination (my comment: transamination- The reaction between an amino acid and an -keto acid through which the amino group is transferred from the former to the latter; in certain cases the reaction may be between an amino acid and an aldehyde).


The capacity for change and adaptation in skeletal muscle has been termed plasticity. Skeletal muscle has an enormous capacity to adapt to stress. Although the adaptive response can be addressed at many different levels, the common process remains the same; a system is stressed, the stressor is sensed, the sensing triggers a response, and the response is designed to bring about change to minimize the perturbation from homeostasis caused by the original stress.

Resistance exercise stimulates mechanoreceptors that trigger a rapid increase in transcription (my comment: transcription- process occurs in nucleus where messenger RNA copies a segment of DNA to be carried to cytosol for protein synthesis) of new messenger RNA and the translation (my comment: translation is a process where the genetic message picked up from nuclear DNA by messenger RNA is transformed into the action of protein synthesis on the ribosomes; translation involves three processes initiation, elongation, termination) of already present mRNA. However, also important is the increase in the transcription and translation of proteins such as growth factors that signal a prolonged (up to 72 h) anabolic response to exercise. These responses create an adaptive potential; however, like any metabolic reaction, the proper substrate must be provided (my comment: nutrition needs to be adequate).

The use of stable isotopes (my comment: excerpt from Body Maintenance and Repair: how food and exercise keep the musculoskeletal system in good shape Michael J. Rennie- Stable isotopes are useful because by definition they do not spontaneously decay to release damaging ionization, and stable isotopes of nitrogen and oxygen are useful as biological tracers because they do not exist in a long-lived form as radioactive isotopes. For example, we have given stable isotope-labelled tracers to pregnant women to measure amino acid flux across the placenta and into babies just before birth (Chien et al. 1993), something that would be unethical with radioactive tracers.) has increased understanding of the adapted response of muscle to mechanical loading. After a bout of heavy resistance training, mixed muscle protein synthesis is increased for up to 48 h. Similarly, after a bout of exercise that is best described as strenuous we reported increases in myofibril protein synthesis that peaked at 24 h and remained elevated at 72 h. Interestingly, over the same period after exercise, the muscle extracellular matrix and tendon increased protein synthesis in a similar pattern.

Another important distinction regarding specificity is that, as opposed to the systematic response of feeding on all skeletal muscle, physical activity only stimulates a response in the stimulated muscle; hence, the response is a local rather than a systemic one (my comment: sure you have heard squatting will make your arms, back and everything else big. Big problem where is the mechanical stimuli for that particular bodypart?)

When considering the process of protein synthesis, the importance of AA as building blocks of protein is appreciated. However, less appreciated is the role of energy in the protein synthetic process, which may be as important as protein intake for maintaining lean body mass (my comment: or gaining LBM, hard to gain muscle tissue while eating nothing but protein and green stuff, generally not enough calories – seems to be common practice of many trainees).

In the basal state, isolated cells use more ATP for muscle protein synthesis than any other cellular process and can account for 20% of resting energy expenditure.

Although current protein recommendations are based on absolute quantities (g/kg bdwt/ per day) and were made assuming energy balance, protein requirements should not be considered in the absence of energy status (my comment: or carbohydrate status).


In the period after exercise without nutrient provision, protein synthesis and protein breakdown are increased compared with the 12-hr fasted reference values indicating that there is a stimulus and remodeling (increase in synthesis and breakdown) response, although net balance does not improve to a positive balance. When there is an exercise stimulus with post exercise AA feeding, protein synthesis increases more than that after exercise or AA feeding alone, and protein breakdown remains similar to exercise without feeding. Because there is an increase in protein synthesis above the rate observed after exercise but not AA provision, it is apparent that the provision of AA enhances protein synthesis. In addition, although protein breakdown is increased, it does not increase more than the fasted exercise response, consistent with an optimization.

Providing nutrition after physical activity takes advantage of the anabolic signaling pathways that physical activity has initiated by providing AA building blocks and energy for protein synthesis (my comment: you are wasting time training for skeletal muscle tissue gains if nutritional protocol sucks).

It has been reported that, as opposed to myofibrillar protein synthesis, intramuscular connective tissue is not responsive to nutrition.

The experiments that concluded that collagen was not sensitive to nutrition measured myofibrillar and collagen protein synthesis rates at rest before and after AA feeding. In both studies, myofibrillar protein synthesis increased with provision of AA, whereas collagen protein synthesis did not. As stated, feeding stimulates a transient storage phenomenon in the skeletal muscle protein reservoir. However, muscle collagen is not a reservoir of AA because it cannot afford changes in protein content in the same manner that contractile and other muscle proteins can. Therefore, it is not surprising that skeletal muscle collagen synthesis did not increase.

Four studies have examined collagen protein synthesis in the muscle after and acute bout of exercise. All four of these, studies were performed in the fed state; in all cases, muscle collagen protein synthesis increased in a magnitude similar to muscle protein synthesis.

In the rested state, provision of AA stimulates storage as skeletal muscle protein but not collagen; after exercise, it is providing the building blocks to take advantage of an adaptive response in both tissues (my comment: proper exercise regimen in accordance with proper nutrition status has potential to do more than just enhance skeletal muscle tissue, when you think of some of the positive structure strengthening effects of resistance training consider the importance effects on other tissues like bone, tendon, cartilage and so on).

It is usually accepted that insulin inhibits muscle protein breakdown (my comment: has been shown in numerous studies); however, insulin’s role in MPS is less clear.

Table 1. Muscle protein synthesis responses with variation in insulin, AA, and energy in human subjects

Insulin AA Energy Protein Synthetic rate
Low High Adequate Increase
High Low High No increase
High High Low Increase
High Low or High Low Increase with high AA only

(my comment: got to have adequate AA to enhance MPS regardless of insulin or calorie levels)


At low concentrations of insulin (5-7 mU L) and adequate glucose (5.4 mM), a systemic AA infusion stimulates muscle protein synthesis. Recently, Bell et. al. demonstrated that systemic infusion of insulin and energy, without infusion of AA, did not increase muscle protein synthesis. In the same study, local infusion of insulin, to maintain AA concentration, with low energy, stimulated muscle protein synthesis. These results demonstrate that AA are the primary factor driving an increase in muscle protein synthesis; although insulin and energy (glucose) can modulate response, they alone are not sufficient to support a full synthetic response. A recent study by Fujita et al. confirms this in that hyperinsulinemia only stimulates an increase in muscle protein synthesis when accompanied by increased AA delivery. In reality, a mixed meal, the kind people normally consume, will contain all three dietary macronutrients for optimal protein storage (my comment: the composition of the meal will have a big influence of insulin secretion, specific foods vary in insulin stimulation, hint not only carbs stimulate insulin secretion some amino acids cause significant stimulation as well).

In fact, the robust increase in muscle protein synthesis seen post exercise in the fasted state, when insulin is quite low (<8-10 mU L), lends some support to the concept that insulin does not have to be elevated for a rise in MPS to occur. However, as discussed above, AA, energy, and perhaps higher insulin concentrations would maximize the adaptive response.

As proposed, the adaptive response to exercise is ultimately dependent on the provision of AA building blocks for protein synthesis and carbohydrate, or possibly lipid, for an energetically expensive process. Therefore, studies that have examined factors such as increased mRNA or the up-regulation of translation initiation factors in skeletal muscle in response to exercise are indicative of adaptive potentials and not outcomes.

My thoughts: This paper presented us with information that is very applicable to everyday training conditions. There must be a sufficient quantity of indispensable amino acids present to enhance MPS. Surprising to some people is the actual role insulin plays in protein balance. Insulin does not cause the same affects in humans as it does rats, mice, pigs (growing animals generally used for research). Below is an excerpt from Body Maintenance and repair: how food and exercise keep the musculoskeletal system in good shape MJ. Rennie.

The nature of the involvement of insulin, classically thought of as the most important anabolic hormone, is bizarre because it appears that in adult humans insulin does not do what it does in the growing animals traditionally used for metabolic research, such as rats, mice and even pigs. In people, it appears that it is possible to stimulate muscle protein synthesis by supplying exogenous amino acids alone while maintaining (using insulin clamp techniques) basal blood insulin concentration at the overnight fasted level (Cuthbertson et al. 2004; Fig 2). Furthermore, if amino acids In amounts capable of causing a maximal response in protein synthesis are given, adding further insulin has no further stimulatory effect on protein synthesis but does sharply reduce protein breakdown (Greenhaff et al. 2005). When we use the insulin clamp technique, utilizing octreotide to inhibit insulin secretion and then replacing insulin to desired levels, we also inhibit the secretion of growth hormone and any subsequent changes in insulin like growth factor 1. Thus it appears that the amino acid stimulation of muscle protein synthesis is also independent of the increases in growth hormone or IGF-1 which would normally occur in the unclamped situation.

On a final note, a sufficient amount of calories, insulin and amino acids are necessary to maximize the response stimulated by resistance training.


Copyright 2007 Jamie Hale


Gropper, S. (2000). The Biochemistry of Human Nutrition: A Desk Reference. Wadsworth.

Hale J. (2007). Protein Essentials. MaxCondition Publishing.

Miller BF. (2007). Human Muscle Protein Synthesis After Physical Activity and Feeding. Sport Sci. Rev. , Vol. 35, No 2, pp. 50-55, 2007.

Rennie MJ. (2005). Body Maintenance and repair: how food and exercise keep the musculoskeletal system in good shape. Exp Physiol 90.4 pp.427-436.

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