Acute tryptophan depletion in bulimia: effects on large neutral amino acids

Acute tryptophan depletion, which may reduce brain serotonin synthesis in humans, was evaluated in bulimic and normal subjects assessing its effects on the plasma ratio of tryptophan to the sum of the other large, neutral amino acids (TRP/sigma LNAA). Thirteen bulimic and 9 control women ingested an amino acid mixture containing either 2.3 g (control mixture) or 0 g of tryptophan (active mixture), in combination with 100 g of the other amino acids. Six healthy male volunteers were also studied, using a similar mixture containing 4.6 g of tryptophan. Bulimic and control women both experienced sizable reductions in the plasma TRP/sigma LNAA ratio, compared to baseline values, for both the active mixture (10% of baseline) or the control mixture (45% of baseline). For bulimic women, the active mixture produced a significant increase in fatigue and a trend toward increased anxiety and indecisiveness. The control mixture did not maintain baseline TRP/sigma LNAA ratios so we identified a control amino acid mixture that does not cause a drop in the plasma TRP/sigma LNAA ratio when ingested (4.6 g tryptophan in combination with 100 g of other amino acids). An oral, tryptophan-deficient amino acid mixture produced acute, substantial reductions in the plasma TRP/sigma LNAA ratio in all subjects, suggesting that the treatment should reduce brain tryptophan uptake and serotonin synthesis. A control mixture containing tryptophan was also identified that maintains the plasma TRP/sigma LNAA ratio at pretreatment values.