Rationale: Prior studies had suggested (a) that a lessened ability to clear
ingested forms of the large neutral amino acid (LNAA), phenylalanine (Phe)
, was associated with having tardive dyskinesia (TD), and (b) that greater
availability of a group of LNAA, the branched chain amino acids (BCAA), con
comitant with the lower availability of Phe to the brain are associated wit
h :I decrease in TD symptoms. The present study was then conducted to test
whether increasing the daily intake of the BCAA would decrease the symptoms
of TD. Methods: A 2-week trial of a BCAA medical food administered three t
imes a day was conducted in nine men with long neuroleptic treatment histor
ies. Frequency counts of TD movements were collected by videotape throughou
t the trial and these tapes were analyzed in blind random sequence for both
patient and time for TD symptom level changes subsequent to completion of
the trial. Plasma levels of the LNAA were also collected throughout the tri
al. Results: A statistically significant decrease in the level of TD sympto
ms was observed for the sample. The symptom changes were also clinically si
gnificant in that six of the nine subjects had symptom decreases of at leas
t 58%, with all subjects having a decrease of at least 38%. BCAA administra
tion increased plasma BCAA concentrations aad BCAA/LNAA ratios and decrease
d plasma Phe concentrations and the Phe/LNAA ratio. Analyses indicated a st
rong significant correlation between the percent increase in the plasma BCA
A values at the first administration and the percent improvement in TD over
the trial in eight of the nine subjects. Conclusions: The BCAA show promis
e as a treatment for TD. The decrease in TD symptoms seen in the trial may
have been modulated by the BCAA treatment-induced increased. availability o
f the BCAA and decreased availability of Phe to the brain.