Branched Chain Amino Acids- Benefits and Role as Supplements

Branched chain amino acids or BCAA are three essential amino acids namely valine, leucine, and isoleucine.

These are called essential because these cannot be produced by the body and must be obtained from food.

There is a total of 20 amino acids in our body. Out of these nine are essential. Out of these three have branched-chain structures.

Amino acids are building blocks of proteins, which are the building blocks of every cell, tissue, and organ. Both play a crucial role in metabolism too.

Branched chain amino acids have been studied in a number of disorders like liver cirrhosis, renal failure, sepsis, trauma, burn injury, and cancer.

Branched chain amino acids are also thought to be important for muscle building as they are thought to promote anabolic pathways.

There potential health improvement effects are thought to improve cachexia, prevent or treat hepatic encephalopathy, and decrease fatigue during exercise, promote wound healing, and stimulate insulin production.

But, there is no consensus, until today, regarding their use as nutritional supplements.

There is no recommended BCAA dosage. But they do form the part of the protein diet which has different recommendations for a different set of populations.

Sources of Branched Chain Amino Acids

A protein-rich diet is a good source of branched chain amino acids as these are available in a wide variety of foods.

Meat, poultry, and fish
Dairy products
Eggs
Nuts
Soybean and its products
Legumes
Greek yogurt

Metabolism of Branched Chain Amino Acids

Most of the amino acids are initially metabolized in the liver. But in the case of branched chain amino acids, the initial metabolism does not take place in the liver.

This is due to the fact that in liver there is a low hepatic activity of branched-chain-amino-acid aminotransferase.

Therefore, after ingestion, branched-chain amino acids increase rapidly in the systemic circulation.

The initial site of metabolism is the skeletal muscle which results in the formation of glutamate and the corresponding branched-chain keto acids

Glutamate then acts as an amino group source to form alanine (ALA) from pyruvate. It also acts as a substrate for ammonia detoxification and converts to glutamine during the process.

Further metabolism occurs in the liver, kidneys, and heart.

Thus muscle and liver play a dominant role in branched chain amino acid metabolism.

Effect of Diet on BCCA Levels

Starvation
- Brief starvation increases BCAA concentrations
  - Increased protein breakdown
  - Reduced protein synthesis in muscles
- Prolonged starvation lowers the BCAA concentration
Low-protein diet
- Lower the plasma BCAA concentrations
- BCAA or BCKA supplementation is recommended when a low-protein diet is prescribed to patients as in chronic renal failure.
High-protein diet
- Increase protein synthesis
- Decrease protein breakdown
- Reduce fat accumulation
- Overall effect
  - Builds muscle mass in athletes
  - Prevent muscle wasting

Different Conditions with Altered BCCA Levels

Decreased BCCA Levels

Liver cirrhosis
- Play a role in hepatic encephalopathy and muscle wasting
- An inverse relationship between plasma ammonia and branched chain amino acids concentration in these patients
- Supplementation has the potential for [But no strong evidence yet]
  - Positive effect on ammonia detoxification
  - Liver regeneration and hepatic function
  - Glucose metabolism
  - Physical and mental fatigue
Urea cycle disorders
- Enzymatic defects in the ammonia detoxification
- Leading to low levels of urea and high levels of ammonia
- Theoretical rationale to use BCAAs as a therapeutic agent but not much research yet
Chronic renal failure
- Decreased branched chain amino acids and branched chain keto acids levels [also other nonessential amino acids] in the blood
- Reduced concentrations of valine in muscles
  - Acidosis
  - Effects of glucocorticoids [there is decreased excretion]
  - Decreased intake of proteins
- Supplementation may maintain protein balance and at the same time allow low protein diet without affecting urea levels

Increased BCAA Levels

Type 1 diabetes
Type 2 diabetes
Obesity

Inconsistent alterations in BCAA levels

Exercise
- May increase decrease or remain unchanged
- The rationale for supplementation [but no benefits noticed in studies]
- Benefits suggested
  - Muscle protein synthesis
  - Fatigue recovery
  - Exercise-induced muscle damage
Systemic inflammatory response syndrome [SIRS]
- Seen in sepsis, burn injury, trauma, and cancer
- All are hypermetabolic states
- BCAAs act as a significant energy substrate
- Change in levels is not consistent due to multiple influencing factors
- BCCA supplementation thought to be beneficial in SIRS but no evidence in most cases
- Definite benefit was seen in traumatic brain injury

Functions of the BCAA

Participate in protein metabolism
- Serve substrates for protein synthesis
- Stimulate protein synthesis
- Inhibit protein degradation
Influence neurotransmitter levels in the brain with effects on behavior and brain function.
Upregulate glucose transporters and activate insulin secretion
Increase levels of Alanine and Glutamine in metabolism
- ALA is the main gluconeogenic amino acid
- GLN is essential for
  - Immune system
  - Glutathione production
  - Maintenance of acid-base balance by the kidneys
  - Expression of heat shock proteins.
- Other effects [Reported by studies, not established]
- Improvement of breast health and quality of breast milk
- Intestinal development
- Mitochondrial biogenesis and oxidative stress

BCCA Supplements and Their Health Benefits

Potentially, there are multiple health benefits of BCAAs. But it must be emphasized that while few studies have pointed out at the benefit, it has not been established beyond doubt that supplementation works.

So as of now, there is no condition for the recommendation of branched chain amino acids.

The following are the situations where supplementation of BCCA is recommended but whether they actually help or not is still under evaluation.

Improvement in exercise performance by reducing exercise fatigue
Lean muscle mass
- BCCA increase protein synthesis and decrease fat accumulation
- Increase in non-fat mass
To prevent muscle wasting during an illness like cancer, chronic renal failure

In liver disease
- BCAA supplementation may benefit people with liver disease by lowering ammonia nd thus decreasing hepatic encephalopathy risk
- They also prevent muscle wasting.

All said, branched chain amino acid supplements are available commercially and people use them based on oral recommendations and some studies with positive results.

But the final verdict is still awaited and they are not recommended for clinical use.

References

Fischer JE, Funovics JM, Aguirre A, James JH, Keane JM, Wesdorp RI, et al. The role of plasma amino acids in hepatic encephalopathy. Surgery. 1975;78:276–90.
Nishitani S, Takehana K, Fujitani S, Sonaka I. Branched chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2005;288:G1292–300.
Zhang S, Zeng X, Ren M, Mao X, Qiao S. Novel metabolic and physiological functions of branched chain amino acids: a review. J Anim Sci Biotechnol. 2017;8:10.
Holecek M. Three targets of branched-chain amino acid supplementation in the treatment of liver disease. Nutrition. 2010;26:482–90.
Kasperek GJ, Dohm GL, Snider RD. Activation of branched-chain keto acid dehydrogenase by exercise. Am J Phys. 1985;248:R166–71.
Bower RH, Kern KA, Fischer JE. Use of a branched chain amino acid enriched solution in patients under metabolic stress. Am J Surg. 1985;149:266–70.
Choudry HA, Pan M, Karinch AM, Souba WW. Branched-chain amino acid-enriched nutritional support in surgical and cancer patients. J Nutr. 2006;136:314S–8S.

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