consumption of a protein-free meal increases the concentration of tryptophan in blood relative to that of the other LNAAs. The mechanism of action of this influence involves the stimulation of insulin release by dietary carbohydrate. Insulin stimulates the release of nonesterified fatty acid (NEFA) molecules from the serum carrier protein, albumin, and their subsequent uptake by adipocytes. The amino acid tryptophan, which has an affinity for albumin, binds in place of the NEFA. As a result, the total serum tryptophan concentration remains constant (unlike the concentrations of other amino aids, which decrease in response to insulin), and the bound tryptophan is able to enter the brain. In contrast, consumption of a high-protein meal results in a decrease in brain tryptophan and serotonin levels because the other LNAAs, which compete with tryptophan for binding to the LNAA transporter and thus for transport to the brain, are present in higher concentrations in dietary protein than is tryptophan (Fernstrom, 1990). As a result, serotonin synthesis is modified in several brain regions, including the hypothalamus and cerebral cortex. Thus, brain serotonin synthesis may be modulated by the protein-to-carbohydrate ratio of the overall diet or a recent meal.

To date, it is not known whether meal-related changes in serotonin production influence brain functions, but a number of studies have linked the changes in serotonin synthesis that follow the administration of tryptophan or its LNAA competitors to functional effects. In laboratory animals, serotonin neurons are most active when animals are awake and physically active (Jacobs and Fornel, 1993) and play an important role in channeling sensory information to the brain (Messing and Lytle, 1977; Walters et al., 1979).

Of particular relevance to the military, Lieberman notes, is the observation that tryptophan administration produces "mental fatigue" and has been used to promote sleep. Administration of tryptophan is also reported to reduce pain sensitivity (Lieberman et al., 1983; Seltzer et al., 1983). A decade ago, significant toxicity was attributed to tryptophan supplements, apparently due to a contaminant that survived the purification process for the amino acid (Hartmann and Greenwald, 1984; Lieberman et al., 1985).

Relatively little is known about how a reduction in serotonin synthesis might influence performance. The administration of an amino acid mixture that should reduce brain tryptophan levels and serotonin synthesis has been found to promote aggressiveness (Cleare and Bond, 1994) and depression (Delgado et al., 1990) in human subjects. These findings suggest that the changes in brain serotonin synthesis that accompany the ingestion of normal foods may produce similar, though less remarkable, effects on these behaviors (because meals cause smaller changes in serotonin than those produced by amino acid treatments). At present, no data exist that evaluate the magnitude of such effects.

Chronic, substantial reductions in protein intake can reduce brain tryptophan levels and serotonin production in laboratory animals (Fernstrom and Wurtman, 1971), with the ingestion of proteins naturally low in tryptophan