LEUCINE AND MUSCLE PROTEIN SYNTHESIS

Supplemental Leucine and Protein Synthesis Post-Exercise

Hannah Brune and Jessica Brown

Miami University of Ohio

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

Abstract

This paper explores five published articles that report on results from research conducted

on the supplementation of leucine and its role in muscle protein synthesis. For this paper, the

focus will be on the health impacts of leucine supplementation on individuals post-exercise,

particularly in terms of muscle mass. This led to conclusions based on the dosage of leucine

supplementation as well as the type of leucine supplementation. Each article discusses leucine

supplementation but vary in terms of which aspects of it are explored. Cermak et al. explores

protein supplementation and the adaptive response of skeletal muscle to resistance-type exercise

training. Duan et al. discusses nutritional and regulatory roles of leucine in muscle growth and

fat reduction, an important aspect for diseases like heart disease, type II diabetes, etc. Garlick

and ​The Journal of Nutrition​ engage in studies based on the myths of very high doses of leucine

supplementation and how it affects muscle protein synthesis. Koopman et al. explore how

muscle protein synthesis may be stimulated by the co-ingestion of protein and leucine in young

and elderly men. Finally, Reitelseder et al. sought out to compare muscle anabolic responses of

leucine-enriched whey protein and leucine-enriched casein protein in muscle protein synthesis.

Post-exercise protein supplementation promotes muscle protein synthesis, but what kind and how

much of it? What about protein degradation? How is insulin sensitivity and glucose metabolism

affected? Further research is always beneficial when considering the health and of a certain

population as well as a newly developing field of dietetics.

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

Introduction

The ketogenic branched chain amino acid, leucine, has been historically found to help

increase muscle protein synthesis in athletes as well as in older adults with diseases causing

muscle to break down at an alarming rate, such as cancer, acquired immunodeficiency syndrome

(AIDS), type II diabetes, or even sepsis (Duan et al. 2015). Leucine takes part in numerous

cellular processes including the ubiquitin proteasome pathway and the mTOR pathway to help

combat such breakdown and increase muscle protein maintenance and synthesis (Duan et al.,

2015). Along with this, specific uses of leucine supplementation allows athletes to reach the

muscle mass they desire in addition to increasing their power in targeted resistance exercises by

increasing strength. It has been proposed that a resistance training athlete can ingest a specific

amount of a general protein supplement during the exercise recovery period to increase muscle

protein synthesis, thus leading to the desired muscle growth by the athlete (Cermak et al., 2012).

While most studies focus on the addition of protein to the protein already consumed in the diet,

the question of how much of the supplement should be taken, the content percentage of leucine

in the supplement, and what form of protein the supplement should be in (i.e. whey, casein, or

essential amino acids) is ongoing (Cermak et al., 2012). Current studies surround how a protein

supplement in general does allow for greater synthesis of muscle protein due to the cellular

processes the protein's amino acids have a role in and the processes they inhibit or permit to

perform. Therefore, supplementation of the branched chain amino acid, leucine, may provide a

signaling role in the substantial increase of muscle protein synthesis to allow the average healthy

athlete to gain fat free mass greater than those who do no not supplement with it.

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

Results

The research on leucine currently focuses on components including quantity of which

should be ingested, types of food where leucine can be ingested, the interplay of leucine and

specific nutrients and hormones to up-regulate muscle protein synthesis, and the age factor to

how the body can increase muscle when presented with leucine in the diet or in supplement

form. It is firstly important to examine how leucine can affect cellular processes involved in

muscle protein synthesis to thoroughly understand its role. The Ubiquitin-Proteasome pathway

and its interplay with leucine supplementation allows for protein to remain intact, instead of

being broken down for energy use. This is specifically valuable when an individual is not taking

in sufficient amounts of the other two macronutrients, carbohydrates and fats.

Carbohydrates are the bodies first source of energy, provided that there are sufficient

stores in the body already existing and that the individual is intaking sustainable amounts in a

balanced diet. When an individual has type I or II diabetes mellitus, this becomes increasingly

more difficult as the body is either unable to use the insulin hormone existing in the body or is

unable to synthesize enough insulin to breakdown the carbohydrates in the diet. Occasionally the

diabetic individual can fall into a state called diabetic ketoacidosis (DKA), where the body has

high concentrations of ketones in the body due to it only being able to break down fats for energy

since the insulin designed to breakdown carbohydrates is unable to do its job. In the most severe

cases, those in DKA typically lose muscle mass by breaking down protein substrates into its

amino acids for body use (Mitch et al. 1999). This occurs via the ubiquitin-proteasome pathway,

where leucine acts as an inhibitor when in abundance. Leucine oxidation and metabolism

generates a metabolite called HMB, or beta-hydroxy beta-methylbutyrate, which lessened the

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

muscle proteolysis and depression of muscle protein synthesis in elder individuals and those with

illnesses such as DKA or cancer (Gropper, Smith & Carr, 2018). HMB, along with the whole

leucine BCAA, also has the ability to stimulate muscle synthesis to build muscle mass in

conjunction with their power to combat depression of muscle protein synthesis (Gropper, Smith

& Carr, 2018). Therefore, when an athlete intakes a protein supplement containing the leucine

BCAA, they give their body potential to steer away from muscle breakdown and promote muscle

synthesis. This does not necessarily mean that a diabetic athlete will not fall into DKA, as the

illness is caused by ketones in the body and is inevitable once the levels reach a specific amount.

They will, however, lessen the overall risk for protein breakdown in severe levels.

The mammalian target of rapamycin (mTOR) pathway is activated and regulated by

leucine and insulin, allowing for anabolism of protein in muscle (Duan et al., 2015). Once

leucine is available and enters the cell, the mTOR pathway is stimulated causing protein

synthesis in skeletal muscle and adipose tissue and further activation of cellular energy

metabolism for fatty acids oxidation to lessen fat mass in the body ensues (Duan et al., 2015).

The body needs plentiful nutrients from the diet to support this process as well as mRNA

translation to generate protein in the muscle. Because of this, the net synthesis of proteins in

muscle is only enhanced in the presence of leucine; it may only occur efficiently when the diet is

strong in micronutrients and supported by hormones such as insulin (Duan et al., 2015).

Muscle protein turnover after an individual participates in resistance exercise affects the

amino acid availability in the body. The effects of different protein sources in regards to

resistance exercise may point direction to which source provides the best supplementation in

order to build muscle mass and stimulate muscle protein synthesis (Reitelseder et al., 2011).

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

Muscle mass not only is important to musculoskeletal health, but it is also a major site of

metabolism, as it holds amino acids needed in stressful, catabolic, situations (Reitelseder et al.,

2011). The response to resistance exercise and weight training is a prime example of this. When

more force or weight is added to the exercise, the stress induced on the body’s muscle prompts it

to increase muscle mass in order to handle such weight in the future. Enhancing this feature can

be done with supplemental leucine. Therefore, participating in resistance exercise then adding in

an amino acid/protein supplement increases muscle protein synthesis, further increasing muscle

mass and strength to perform exercises.

Protein forms is a very important component in how efficiently protein synthesis goes.

Whey is considered a “fast” protein and casein is a “slow” protein due to their rates of digestion

and absorption (Reitelseder et al., 2011). Following protein intake, leucine concentrations peak

and then return to baseline values. However, these concentrations of leucine significantly

increase after intake of whey compared to casein in a short amount of time, whereas casein has a

prolonged increase (Reitelseder et al. 2011). As a fast-digested and absorbed protein, whey

elicits a strong response to muscle protein synthesis after a combination of its intake and

resistance exercise. Due to the difference in digestion and absorption of different proteins, a

combination of whey and casein would be the best choice postexercise because whey stimulates

muscle protein synthesis due to its high digestibility and concentrations of insulin/amino acids,

while casein provides amino acids for a long period of time (Reitelseder et al., 2011). Milk

contains both whey and casein, and is a very optimal choice as an immediate intake following

resistance or heavy exercise.

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

To best exemplify this statement, the Hartman et al. study showed how beneficial adding

milk during the exercise recovery period can successfully increase muscle protein synthesis.

Researchers trained male participants with a weight training regime. This regime includes three

forms of exercises: pulling movement such as seated lateral pulldown, pushing movement such

as military press, and leg exercises such as a 45 degree leg press (Hartman et al., 2007).

Participants completed 20 sessions of each form by the end of the study where they increased

intensity as the study furthered in terms of repetition and weight. Protein sources had three

groups: ones who consumed fat-free cow’s milk or fat-free soy milk with the same amount of

macronutrients (17.5 g protein, 25.7 g carbohydrate, and 0.4 grams of fat) and the placebo group

drank fluid containing only carbohydrate (Hartman et al., 2007). These beverages were provided

immediately after the workout and 1 hour post-workout. The milk group had a substantial

increase in fat and bone free mass, averaging out at a gain in 6.2 kg of muscle. They also had a

decrease of 5.5 kg of fat mass with that and an increase of 1.7kg in bone mineral content. in the

soy group, participants had an increase of 4.4 kg of fat and bone free mass with a 1.5 kg loss of

fat mass and 1.8kg of bone mineral content. Lastly, in the placebo, they only gained 3.7 kg of fat

and bone free mass with a 3.4 kg fat loss and 0.6 kg increase in bone mineral content (Hartman

et al., 2007). These findings support how drinking fat-free milk as the source for leucine directly

after the workout can help increase fat-free mass in the body of a healthy individual, similar to

what was found in the Reitelseder et al. study as well as in the Koopman et al. study.

When carbohydrates are ingested, protein synthesis is not affected, although protein

degradation is stimulated (Koopman et al., 2006). When combined with leucine, net muscle

protein formation has been shown to increase compared to a drink or supplement containing only

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

carbohydrates. Whole-body protein turnover is at its optimal balance when individuals who

partake in moderate-intensity physical exercise including weight lifting and light cardio drink a

supplement containing carbohydrates, protein, and leucine (Koopman et al., 2006). Interestingly

enough, the whole body breakdown of protein 6 hours after exercise was lower in groups who

drink a drink with the three components than in those who only drink fluids with carbohydrates

(Koopman et al., 2006). Younger individuals doing so have also a higher synthesis response to

the supplement than elders. This may be attributed to the blunted insulin response in the elderly,

as the leucine and insulin interplay has a large role in muscle protein synthesis (Koopman et al.,

2006).

Amino acid and insulin concentrations in regards to muscle protein synthesis and

resistance training leads to an increased phosphorylation, which shows that excess amino acids

post-exercise induces proper stimulation (Reitelseder et al., 2011). This stimulation increases

muscle protein synthesis rates and inhibits muscle protein breakdown (Cermak et al., 2012).

These actions result in a net muscle protein gain. However, too much protein (leucine)

supplementation could lead to irregular glucose metabolism (Garlick, 2005). This is because high

leucine can inhibit protein degradation in the muscle due to the increase in insulin that occurs

from the leucine dosage (Garlick, 2005). Therefore, the role of leucine is to work with insulin to

activate the stimulation of muscle protein synthesis when both amino acids and energy from food

are available (Garlick, 2005). This is only activated when the conditions of amino acids (leucine)

and energy (insulin) are ideal. Leucine becomes an enhancer of insulin sensitivity when it is

supplemented in high doses over a long period of time (Garlick, 2005). An overstimulation of

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

leucine occurs, which leads to abnormal glucose metabolism, especially because muscle protein

synthesis and insulin share common signaling pathways (Garlick, 2005).

Conclusion

In order to gain a complete understanding of the impact that leucine supplementation has

on muscle protein synthesis, it is necessary to conduct studies that explore all aspects of the type

of protein that contains leucine, as well as the dosage of leucine supplementation. The effects of

leucine supplementation on muscle protein synthesis are clearly beneficial in terms of muscle

mass gain and fat loss, however, the insulin sensitivities that occur due to high doses of leucine

can become detrimental to one’s body. As each study continues to further research, it is

important to stress the proper recovery of post-exercise so that the supply of BCAA’s are

replenished. Since protein and BCAA are diminished as a result of exercise, muscle protein

breakdown occurs. In order for muscle growth to occur, muscle protein synthesis must be

stimulated and take over this breakdown. The role of leucine and BCAAs are important for

triggering this increased rate of protein synthesis and decreasing protein degradation in skeletal

muscle.

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LEUCINE AND MUSCLE PROTEIN SYNTHESIS

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