Overview
Isoleucine is an essential amino acid that belongs to the branched-chain amino acids group along with leucine and valine. It cannot be synthesized by the human body and must be obtained from dietary sources. Isoleucine is a nonpolar, hydrophobic amino acid and is both glucogenic and ketogenic. It plays an important role in protein synthesis, muscle metabolism, hemoglobin formation, energy production, and immune function.
The physiologically active form is L-isoleucine, which participates in metabolic pathways where its catabolism produces acetyl-CoA and propionyl-CoA that enter the Krebs cycle or ketone body formation, supporting cellular energy needs.
Symptoms
Deficiency of isoleucine leads to muscle atrophy and wasting, generalized weakness, fatigue, tremors, and poor exercise tolerance. Affected individuals may experience hypoglycemia, impaired immune response, confusion, dizziness, irritability, depression, and anemia. In severe deficiency, neurological symptoms such as involuntary shaking and reduced coordination may occur.
Excess isoleucine or toxicity is associated with gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain, along with headache, dizziness, lethargy, fatigue, muscle tremors, seizures, poor feeding, and, in extreme cases, coma.
Causes
Low isoleucine levels are caused by inadequate dietary intake, malnutrition, malabsorption, chronic illness, liver disease, or increased metabolic demand during stress, infection, or trauma. Deficiency may also occur in metabolic disorders affecting branched-chain amino acid metabolism. Elevated levels are seen in inherited disorders such as maple syrup urine disease, where impaired breakdown of branched-chain amino acids leads to accumulation and neurotoxicity. Excess intake through supplementation or impaired metabolism can also result in toxicity.
Risk Factors
Risk factors for abnormal isoleucine levels include poor protein intake, malnutrition, chronic liver disease, metabolic stress, and inherited amino acid metabolism disorders. Infants and children with inborn errors of metabolism are at higher risk of clinically significant abnormalities. Athletes, pregnant women, and individuals in recovery states have higher requirements and are at risk of deficiency if intake is inadequate. Improper sample collection, lack of fasting, hemolysis, or delayed processing can affect laboratory assessment.
Prevention
Prevention focuses on maintaining adequate dietary intake of isoleucine through protein-rich foods such as meat, fish, dairy products, legumes, nuts, seeds, and whole grains.
Early detection and management of metabolic disorders help prevent accumulation and toxicity. In high-risk individuals, nutritional assessment and supplementation, when required, support normal muscle, immune, and metabolic function. Proper laboratory practices, including fasting samples, correct handling, and timely processing, improve diagnostic accuracy and help prevent misinterpretation of isoleucine levels.
