Trait: BCAA metabolism and muscle building
Dr Haran Sivapalan
May 10, 2021
This trait is closely related to your BCAA breakdown trait, with your Insights and Actions more focussed on the impact of BCAAs on building muscle.
Readers are encouraged to visit the BCAA breakdown and BCAAs and Insulin trait articles for further background information.
What are BCAAs?
BCAAs stands for branched chain amino acids. It is the collective name for three particular amino acids (the building blocks of proteins):
These amino acids play important roles in building new muscle proteins, providing energy for muscles and control of glucose metabolism.
Due to these roles, BCAAs are a popular pre-workout supplement, where they are used to stimulate muscle protein synthesis and boost muscle growth, reduce muscle soreness after a workout, and help to prevent fatigue during exercise.
As well as being in various supplements and protein powders, BCAAs are also found in various foods, including: red meat, poultry, eggs, dairy products, nuts, lentils and beans.
The BCAAs are essential amino acids. This means they must be consumed in our diet as we cannot synthesise them ourselves.
- BCAAs refers to 3 essential amino acids: leucine, isoleucine, and valine.
- BCAAs play roles in muscle growth, energy production and glucose metabolism.
- Sources of BCAAs include meat, dairy, eggs, as well as workout supplements (e.g. pre-workout supplements, protein powders).
How do BCAAs affect muscle building?
BCAAs have been shown to enhance the process of muscle protein synthesis – the building of new contractile and non-contractile muscle proteins from amino acids.
As discussed in the Muscle Hypertrophy trait article, in order to gain muscle strength and size, the rate at which we build new muscle proteins (i.e. the rate of muscle protein synthesis) needs to be greater than the rate at which we break down or degrade muscle proteins (i.e. the rate of muscle protein breakdown).
Therefore, by stimulating muscle protein synthesis, BCAAs may assist muscle building. In line with this, a Dutch study found that the rate of synthesis of myofibrillar proteins (myofibrils are components of muscle fibres) significantly increased within the first 2 hours after ingesting 6g of BCAAs.
In particular, leucine is thought to enhance muscle protein synthesis by stimulating a signalling pathway known as the mTOR pathway. We’ve encountered the mTOR pathway before in the Muscle Hypertrophy (mTOR) trait article.
To recap, the mTOR signalling pathway acts as a sensor of the internal and external environment of cells, switching on protein synthesis when conditions are appropriate. One of the appropriate conditions for protein synthesis is having a good availability of amino acids, the building blocks of proteins. When tissue levels of BCAAs (in particular, leucine) increase in conjunction with mechanical stress on muscles, this stimulates the mTOR pathway, resulting in protein synthesis and, if sustained over time, gains in muscle mass.
Source: Torre-Villalvazo, I., Alemán-Escondrillas, G., Valle-Ríos, R., & Noriega, L. G. (2019). Protein intake and amino acid supplementation regulate exercise recovery and performance through the modulation of mTOR, AMPK, FGF21, and immunity. Nutrition research, 72, 1-17.
As well as stimulating muscle protein synthesis, BCAAs have been shown to reduce muscle protein breakdown. For example, studies in human subjects have reported reduced muscle protein breakdown following intravenous infusion of leucine.
Despite their anabolic effects and potential to assist with muscle building, however, high/excessive levels of BCAAs circulating in the bloodstream can actually hamper muscle protein synthesis and muscle gains.
- BCAAs can stimulate muscle protein synthesis, which can lead to gains in muscle strength and size.
- BCAAs, particularly leucine, stimulate the mTOR pathway which regulates protein synthesis.
- BCAAs can also reduce muscle protein breakdown, which can lead to gains in muscle strength and size.
- Excessively high circulating levels of BCAAs can impair muscle gains.
Why do high levels of BCAAs impair muscle building?
High levels of BCAAs circulating in the body can make various tissues, including muscle tissues, less sensitive to insulin. Reduced sensitivity to insulin can, in turn, impair muscle building.
Under normal circumstances, insulin, as well regulating metabolism of fat and glucose, acts as an anabolic hormone that stimulates muscle protein synthesis. Insulin orchestrates its effects in the body by binding to a specialised receptor on the surface of different cells: the insulin receptor.
When insulin binds to the insulin receptor, it activates a signalling pathway known as the PI3K/AKT pathway, which interacts with the mTOR pathway to stimulate muscle protein synthesis.
Source: Makanae, Y., & Fujita, S. (2015). Role of Exercise and Nutrition in the Prevention of Sarcopenia. Journal of nutritional science and vitaminology, 61(Supplement), S125-S127.
When circulating levels of BCAAs in the bloodstream are elevated, however, this can cause excessive stimulation of the mTOR pathway and also inhibition of the insulin receptor signalling pathways. Consequently, tissues in the body (including muscle cells) become less sensitive or “resistant” to the effects of insulin.
Source: Yoon, M. S. (2016). The emerging role of branched-chain amino acids in insulin resistance and metabolism. Nutrients, 8(7), 405.
Insulin resistance caused by high levels of BCAAs therefore makes muscle tissue less sensitive to the anabolic effects of insulin, resulting in reduced muscle protein synthesis. This effect is more pronounced in people performing little to no physical activity, as exercise (particularly resistance exercise) is also a potent activator of the mTOR pathway and muscle protein synthesis.
Source: Melnik, B. C., Schmitz, G., John, S. M., Carrera-Bastos, P., Lindeberg, S., & Cordain, L. (2013). Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status. Nutrition & metabolism, 10(1), 1-6.
High circulating levels of BCAAs can also disturb the fat metabolism of muscles, causing the accumulation of lipid within skeletal muscle. This can worsen insulin sensitivity and impair muscle building.
Another process that is negatively affected by high levels of BCAAs is autophagy. Autophagy refers to a process by which cells “clean out” and remove damaged components/organelles (e.g. mitochondria) and misfolded proteins. This allows cells to regenerate and build new components.
Within muscle tissues, autophagy is shown to be important for preserving muscle mass and maintaining the integrity of muscle fibres. In particular, autophagy is thought to play a key role in muscle adaptations to endurance exercise, such as the renewal of mitochondria.
BCAAs, however, can inhibit autophagy, partly through the mTOR signalling pathway. By inhibiting autophagy and renewal of key cell components in muscle fibres, high circulating levels of BCAAs can impair muscle growth and adaptations to training.
- Insulin is a hormone that stimulates muscle growth.
- High levels of BCAAs can worsen insulin sensitivity, which can impair muscle growth.
- High levels of BCAAs can promote fat accumulation in skeletal muscle.
- High levels of BCAAs can interfere with autophagy – the process by which muscle cells degrade damaged components and lay down new proteins.
How do genes and lifestyle factors affect your circulating levels of BCAAs?
As explained in the BCAA breakdown trait article, variants of the APOA2 gene can affect how effectively you break down BCAAs, which, in turn, can influence your circulating levels of BCAAs.
More specifically, people with the CC genotype (rs5082 SNP) of the APOA2 gene are shown to switch off production of enzymes that break down BCAAs in response to high (>22g/per day) intakes of saturated fat. This, in turn, can lead to higher circulating levels of BCAAs, which can impair muscle building.
Accordingly, people with the CC genotype wishing to optimise muscle building may need to avoid both high intakes of saturated fat and BCAAs. This may be particularly pertinent for individuals adopting a ketogenic diet (which is both high in saturated fat and BCAAs), or those taking BCAA supplements.
In addition to APOA2 gene variants, being overweight, obese, and carrying excessive amounts of visceral fat can also impair BCAA breakdown, leading to high circulating levels of BCAAs and suboptimal muscle building outcomes.
- Certain variants of the APOA2 gene (e.g. rs5082) elevate circulating levels of BCAAs, particularly in response to high intakes of saturated fat.
- People with the CC genotype of the APOA2 gene may need to moderate their intake of BCAAs and saturated fat in order to optimise muscle building.
- Carrying excess visceral fat can also lead to high circulating levels of BCAAs and impair muscle building.
Your BCAA metabolism and muscle building trait
Your BCAAs and muscle building trait analyses both your APOA2 gene variants and your lifestyle survey data (including BMI, body composition, waist circumference, and fasting blood glucose levels).
You will be classified into one of three categories:
- Reduced due to genetics – you carry gene variants linked to reduced BCAA breakdown/metabolism, including those that suppress BCAA breakdown when you consume high amounts of saturated fat. This can impair muscle building, especially with high dietary intakes of saturated fat and BCAAs.
- Reduced due to lifestyle – you do not carry gene variants linked to reduced BCAA breakdown/metabolism, but your lifestyle survey data suggest you are overweight, obese, and/or have poor insulin function (all of which are associated with reduced BCAA breakdown). This can impair muscle building, especially with high dietary intakes of saturated fat and BCAAs.
- Average metabolism – you do not carry gene variants or have lifestyle factors associated with reduced BCAA breakdown/metabolism. Your muscle building potential is less likely to be negatively affected by higher dietary intakes of saturated fat and BCAAs.
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