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4th Amino Acid Assessment Workshop

Branched-Chain Amino Acids and Brain Function

Departments of Psychiatry and Pharmacology, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh PA 15213

²To whom correspondence should be addressed. E-mail: fernstromjd{at}upmc.edu.

Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood–brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose–response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

KEY WORDS: • brain • blood–brain barrier • branched-chain amino acids • tyrosine • tryptophan • serotonin • catecholamines • rat • human • neurological diseases • metabolic diseases • exercise • toxicity

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