What are the branch-chain amino acids (BCAAs)?

What Are Branched-Chain Amino Acids (BCAAs)?

Branched-chain amino acids (BCAAs) are three essential amino acids—leucine, isoleucine, and valine—that cannot be synthesized by the body and must be obtained through diet or supplementation. 1, 2

Chemical Identity and Structure

The three BCAAs are distinguished by their branched aliphatic side chains, which give them unique physico-chemical properties compared to other amino acids 3:

• Leucine
• Isoleucine
• Valine

These amino acids are classified as "essential" because humans cannot produce them endogenously, requiring dietary intake to meet physiological needs 4, 5

Metabolic Characteristics

BCAAs are uniquely metabolized primarily in peripheral tissues (skeletal muscle, adipose tissue) rather than the liver, making them particularly important in conditions of hepatic dysfunction. 2

• Initial catabolism occurs predominantly in skeletal muscle through the enzyme branched-chain aminotransferase (BCAT), which converts BCAAs to branched-chain keto acids (BCKAs) 4, 5
• Further oxidation is regulated by branched-chain α-keto acid dehydrogenase (BCKD), the rate-limiting enzyme in BCAA catabolism 4, 5
• Skeletal muscle serves as the primary site for BCAA metabolism, accompanied by release of alanine and glutamine into circulation 5

Physiological Functions

BCAAs serve multiple critical roles beyond simple protein building blocks:

Protein Synthesis and Muscle Metabolism

• BCAAs, particularly leucine, activate the mechanistic target of rapamycin (mTOR) signaling pathway, which regulates translation initiation and muscle protein synthesis 6
• They can transiently stimulate muscle protein synthesis rates, though less effectively than complete protein sources containing all indispensable amino acids 6
• BCAAs reduce indices of whole-body protein breakdown and muscle protein breakdown 6

Ammonia Detoxification

• BCAAs serve as critical substrates for glutamine synthesis in skeletal muscle, essential for extrahepatic ammonia detoxification in patients with liver disease 2
• During catabolic stress, BCAAs donate amino groups through transamination to produce glutamine and alanine for ammonia metabolism 2

Energy Production

• BCAAs provide an alternative energy substrate, particularly important in cirrhosis where glycogen storage is impaired 2
• They supply nitrogen without requiring hepatic metabolism, supporting protein synthesis in liver and immune tissues 2

Dietary Sources

BCAAs are naturally present in all protein-containing foods, making diverse dietary protein intake the primary recommended source rather than isolated supplementation. 7

• Protein sources include meat, dairy products, and vegetable proteins 7
• The American Association for the Study of Liver Diseases recommends obtaining BCAAs through 1.2-1.5 g/kg/day of total protein from diverse sources rather than long-term isolated BCAA supplementation 7, 1

Clinical Relevance

Altered BCAA Metabolism in Disease States

• In liver cirrhosis: BCAA levels are depleted while aromatic amino acids accumulate, creating a pathological ratio that contributes to hepatic encephalopathy 2
• In chronic renal failure: Enhanced BCKD activity leads to increased BCAA oxidation 5
• In diabetes type 2 and obesity: Decreased BCKD activity contributes to elevated BCAA levels 5
• In maple syrup urine disease: Severely decreased BCKD activity causes dangerous accumulation of BCAAs and BCKAs 5

Therapeutic Applications

• BCAA supplementation at 0.25 g/kg/day (approximately 30-34 g/day) is used as adjunctive therapy for hepatic encephalopathy in cirrhotic patients 1
• BCAA-enriched parenteral nutrition solutions (35-45% BCAAs) are recommended for patients with overt hepatic encephalopathy requiring intravenous nutrition 7
• Long-term supplementation (12-24 months) at 0.20-0.25 g/kg/day has demonstrated benefits in preventing progressive hepatic failure and improving quality of life, though mortality benefit remains equivocal 1

Important Clinical Caveats

Cost and palatability significantly affect patient compliance with oral BCAA supplements, as they are not reimbursed in most countries. 1

In well-nourished patients who achieve adequate protein intake (1.2-1.5 g/kg/day) through diverse dietary sources, supplemental BCAAs beyond this target are not recommended. 7, 1