Use of a dietary manipulation to deplete plasma tyrosine and phenylalanine in healthy subjects

Abstract

The aim of the present study was to lower plasma concentrations of tyrosine, the amino acid precursor of noradrenaline and to determine whether this manipulation impaired noradrenergic function as measured by the evening rise in concentrations of plasma melatonin. Eight healthy volunteers received three drinks: (i) an essential amino acid load with tyrosine, (ii) the same load without tyrosine and its precursor, phenylalanine and (iii) tap water. The tyrosine- and phenylalanine-deficient drink lowered plasma tyrosine by approximately 50% over 5 h. However, this did not alter the evening plasma melatonin levels compared to the other two drinks. The results suggest that amino acid loading produces a modest decline in plasma tyrosine levels but this does not lower noradrenergic neurotransmission in the pineal gland.

Lack of Effect of Tyrosine Depletion on Mood in Recovered Depressed Women

“…Although administration of the BAL mixture increases plasma levels of PHE and TYR, (Sheehan et al, 1996) overall, as found in the present study, it produces some lowering in the plasma ratio of TYR þ PHE : BCAA Montgomery et al, 2003). For reasons that are not clear, the extent of this reduction varies somewhat between studies but it is always substantially less than that produced by the TYR-free mixture.…”

“…For example, using in vivo microdialysis, McTavish et al (1999) found in rodents that while TYR depletion attenuated the release of DA produced by amphetamine, noradrenaline release was unaffected. Similarly in humans, AMPT lowered the night-time release of melatonin, a sensitive marker of noradrenaline release, but TYR depletion did not (Zimmermann et al, 1994;Sheehan et al, 1996). Therefore, while TYR depletion predominantly lowers DA activity, AMPT attenuates both DA and noradrenaline function.…”

“…TYR is a naturally occurring amino acid from which DA, and also noradrenaline, are synthesized. Administration of an amino-acid mixture free of TYR, and of the TYR precursor, PHE, lowers plasma TYR and prevents TYR brain entry by competition at the bloodbrain barrier (Biggio et al, 1976;Moja et al, 1996;Sheehan et al, 1996). The result is a marked lowering in the plasma ratio of TYR and PHE to neutral amino acids, which leads to a reduction in the availability of TYR for brain catecholamine synthesis (Fernstrom and Fernstrom, 1995;McTavish et al, 1999).…”

Acute Serotonin and Dopamine Depletion Improves Attentional Control: Findings from the Stroop Task

“…At 4 h post-ingestion participants completed the Stroop task, which took approximately 10 min. This 4 h latency period for testing was chosen to coincide with the timing of maximal monoamine depletion determined in previous research detailing the time course of monoamine depletion in rats (Bel and Artigas, 1996;McTavish et al, 1999b), human plasma (McTavish et al, 1999b;Moja et al, 1996;Sheehan et al, 1996), and cerebrospinal fluid (Carpenter et al, 1998;Williams et al, 1999). Following completion of the Stroop task, participants were again administered the VAMS to examine mood changes following treatment, and were required to give another sample of blood (12 ml) in order to establish the levels of amino-acid depletion achieved.…”

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

“…The acute phenylalanine/tyrosine depletion (APTD) method was recently developed as a new tool to investigate the effects of catecholamine neurotransmission in humans (Moja et al, 1996;Sheehan et al, 1996;Leyton et al, 2000b). Initial studies suggest that APTD decreases subjective effects of amphetamine (McTavish et al, 1999b;Rot et al, 2003), amphetamine-induced changes in impulse control (Rot et al, 2003), alcohol self-administration in social drinkers (Leyton et al, 2000a), withdrawal-related craving in nicotine-dependent smokers (Casey et al, 2002), and mood both in healthy subjects (Leyton et al, 2000b;Harmer et al, 2001) and manic patients ).…”