Effects of aspartame ingestion on the carbohydrate-induced rise in tryptophan hydroxylation rate in rat brain.

Effects of aspartame (aspartyl-phenylalanine-methylester) on increases in brain-tryptophan level and hydroxylation rate following a high-carbohydrate, protein-free meal were tested. After an overnight fast, rats consumed a protein-free meal containing one of several levels of aspartame. Blood and brain amino acid levels and the in vivo rate of tryptophan hydroxylation in brain were estimated at intervals thereafter. Ingestion of the meal alone increased brain-tryptophan level and hydroxylation rate. Aspartame did not modify these effects, except at doses of 530 mg/kg body weight or more. Results suggest a threshold dose of aspartame can be identified for the rat in single-meal studies above which suppression of carbohydrate-induced increases in brain-tryptophan level and serotonin synthesis occurs. This dose, however, is large and, when corrected for species differences in metabolic rate, is unlikely to be ingested by a human subject as a single load.

Twenty-four-hour variations in rat blood and brain levels of the aromatic and branched-chain amino acids: chronic effects of dietary protein content.

Groups of young adult, male rats were given free access for 12 weeks to a single diet containing either 12%, 24%, or 40% protein (dry weight). At the end of this time, six rats from each diet group were killed every four hours throughout a single 24-hour period, and blood samples and brains were obtained for quantitation of several of the large neutral amino acids (LNAAs). The blood level of each LNAA varied significantly as a function of time of day (tending to be lower during the day than at night) and as a function of dietary protein content (typically rising as protein intake increased). Except for tyrosine and valine, the serum concentration ratio of each LNAA to the sum of the other LNAA (previously reported to be a good predictor of the competitive uptake of each LNAA into brain) and the brain level of each LNAA showed unremarkable variations with time of day and dietary protein content. In contrast, the serum ratios and brain levels of tyrosine and valine did show notable variations at night as a function of dietary protein intake. Together, the results show that within a chronic physiologic range of protein intakes, the serum ratios and brain levels of several large neutral amino acids, particularly tryptophan, bear no relationship to dietary protein level. Though good correlations between these parameters and protein intake were obtained for valine and tyrosine, their physiologic/metabolic significance, if any, is unknown. In general, the data do not support the broad, unvalidated use of serum LNAA ratios in chronic settings as predictors of brain LNAA levels.

Absence of chronic effects of dietary protein content on brain tryptophan concentrations in rats.

Groups of young, adult, male rats were given free access for 2 wk to a diet containing 12, 24 or 40% protein (dry weight). During this period, all animals grew considerably; those consuming the 12% protein diet grew less rapidly than those ingesting the higher percent protein diets. At the end of 2 wk, six rats from each diet group were killed every 4 h throughout a 24-h period, and blood samples and whole brains were obtained for analysis. Serum tryptophan levels were lowest in animals consuming the 12% protein diet, intermediate in rats consuming the 24% protein diet and highest in rats consuming the 40% protein diet (at all times studied). Brain tryptophan levels, however, did not differ significantly as a function of dietary protein content. The ratio in serum of the concentration of tryptophan to the sum of the concentrations of its competitors for brain uptake also was not significantly influenced by dietary protein level. Levels of 5-hydroxyindoles in brain showed significant diurnal variations but no evidence of a significant effect of dietary protein content. Since the ratio of serum tryptophan to its competitors and the levels in brain of tryptophan and 5-hydroxyindoles did not vary as a function of dietary protein intake, the results do not support the view that these variables serve as signals to the brain for regulating long-term dietary protein intake.