:Branch-Chain: Amino-Acids:
Isoleucine, Leucine, Valine

Function: Stress

Branched chain amino acids (B.C.A.A.) are essential amino acids whose carbon structure is marked by a branch point. The BCAAs are valine, isoleucine and leucine. These three amino acids are critical to human life and are particularly involved in stress, energy and muscle metabolism. BCAA supplementation as therapy, both oral and intravenous, in human health and disease holds great promise.

BCAA includes valine, isoleucine and leucine which are branched chain essential amino acids. Despite structural similarities, branch-chain aminos have different metabolic routes, with valine going solely to carbohydrates, leucine solely to fats and isoleucine to both. These amino acids also have different deficiency symptoms. Valine deficiency is marked by neurological defects in the brain, while isoleucine deficiency is marked by muscle tremors.

Many types of inborn errors of BCAA metabolism exist, and are marked by various abnormalities. The most common form is the maple syrup urine disease, marked by a characteristic urinary odor. Other abnormalities are associated with a wide range of symptoms, such as mental retardation, ataxia, hypoglycemia, spinal muscle atrophy, rash, vomiting and excessive muscle movement. Most forms of BCAA metabolism errors are corrected by dietary restriction of BCAA and at least one form is correctable by supplementation with 10 mg of biotin daily.

BCAA are useful because they are metabolized primarily by muscle. Stress state –- e.g., surgery, trauma, cirrhosis, infections, fever and starvation--require proportionately more BCAA than other amino acids and probably proportionately more leucine than either valine or isoleucine. BCAA and other amino acids are frequently fed intravenously (TPN) to malnourished surgical patients and in some cases of severe trauma.

BCAA, particularly leucine, stimulate protein synthesis, increase reutilization of amino acids in many organs and reduce protein breakdown. Furthermore, leucine can be an important source of calories, and is superior as fuel to the ubiquitous intravenous glucose (dextrose).

Leucine also stimulates insulin release, which in turn stimulates protein synthesis and inhibits protein breakdown. These effects are particularly useful in athletic training. BCAA should also replace the use of steroids as commonly used by weightlifters. Huntington's chorea and anorexic disorders both are characterized by low serum BCAA. These diseases, as well as forms of Parkinson's, may respond to BCAA therapy. BCAA, and particularly leucine, are among the amino acids most essential for muscle health.

BCAA are decreased in patients with liver disease, such as hepatitis, hepatic coma, cirrhosis, extrahepatic biliary atresia or portacaval shunt; aromatic amino acids (AAA)-tyrosine, tryptophan and phenylalanine, as well as methionine-are increased in these conditions. Valine, in particular, has been established as a useful supplemental therapy to the ailing liver. All the BCAA probably compete with AAA for absorption into the brain. Supplemental BCAA with vitamin B6 and zinc help normalize the BCAA:AAA ratio.

The BCAA are not without side effects. Leucine alone, for example, exacerbates pellagra and can cause psychosis in pellagra patients by increasing excretion of niacin in the urine. Leucine may lower brain serotonin and dopamine. A dose of 3 g of isoleucine added to the niacin regime has cleared leucine-aggravated psychosis in schizophrenic patients. Isoleucine may have potential as an antipsychotic treatment.

Leucine is more highly concentrated in foods than other amino acids. A cup of milk contains 800 mg of leucine and only 500 mg of isoleucine and valine. A cup of wheat germ has about 1.6 g of leucine and 1 g of isoleucine and valine. The ratio evens out in eggs and cheese. One egg and an ounce of most cheeses each contain about 400 mg of leucine and 400 mg of valine and isoleucine. The ratio of leucine to other BCAA is greatest in pork, where leucine is 7 to 8 g and the other BCAA together are only 3 to 4 g.

In serum, BCAA, particularly leucine, are great producers of energy under many kinds of severe stress, such as trauma, surgery, liver failure, infection, fever, starvation, muscle training and weight lifting. BCAA supplements, while now used only preoperatively for malnourished patients, should be used in all stress situations. For example, BCAA may replace aspirin therapy for fever.

BCAA therapies have great potential in the medicine of the future which seeks better health by imitating natural mechanisms of the body.