Plasma Tryptophan Concentrations Research Articles

Tryptophan and its metabolites in patients on continuous ambulatory peritoneal dialysis and following renal transplantation

Plasma tryptophan (Trp) concentration in its total (TTrp) and non-protein-bound free form (FTrp) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) as well as muscle Trp contents (MTrp) were studied in 12 uraemic patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 10 renal transplant patients, and 10 healthy control subjects. The CAPD patients exhibited signs of muscle weakness, as assessed by dynamometry, and signs of protein malnutrition with a decreased ratio of alkali-soluble protein relative to DNA in muscle as well as low serum albumin concentration. In the uraemic patients TTrp was markedly reduced, whereas in the transplant patients it did not differ from the controls. The FTrp, which was separated by the process of equilibrium dialysis, was less in the uraemic (P < 0.01) as well as transplant patients (P < 0.01) than in the controls. The plasma FTrp/TTrp ratio was increased in the uraemic patients (40 +/- 8%) but less in the transplant patients (16 +/- 4%), as compared to the controls (25 +/- 5%). The uraemic patients had increased plasma concentrations of 5-HIAA, whereas this metabolite could not be found in the plasma of renal transplant patients and healthy controls. MTrp was increased by an average of 33% in the uraemic patients whereas it did not differ between the transplant patients and the controls. The results indicate that the abnormal Trp metabolism in uraemic patients is to a large extent corrected by a successful renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreases of plasma tryptophan concentrations following restricted feeding do not decrease serotonin and its metabolite in rat brain

Rats trained on a restricted feeding (RF) schedule of 4 h/day were killed before (starved) and after (fed) the presentation of food to compare hepatic and brain tryptophan metabolism with feeding (FF) controls. The RF rats exhibited greater holo-tryptophan pyrrolase activity in the liver than FF controls. Holoenzyme activity of starved rats was greater than fed animals. Plasma levels of tryptophan higher in the FF rats were comparable in the starved and fed groups of RF rats. Plasma levels of glucose comparable in the FF and RF fed rats were smaller in the starved animals. Brain levels of tryptophan comparable in the RF fed rats and FF controls were smaller in RF starved rats. Brain concentrations of serotonin (5-hydroxytryptamine) and its metabolite 5-hydroxyindoleacetic acid comparable in the RF starved rats and FF controls were higher in the RF fed rats. Possible implication of the findings in the pathogenesis of food deprivation/starvation related disease, anorexia nervosa is discussed.

Effects of a competitive triathlon on plasma concentrations of tryptophan and branched-chain amino acids

The aim of this work was to determine the acute responses of tryptophan and branched chain amino acids to a triathlon competition. Fourteen male triathletes were studied. All took part in a international triathlon race consisting of 1,5 km swimming, 40 km biking and 10 km running. Venous blood samples were drawn before (-24 h) and after (15 min) the triathlon. Plasma concentration of branched chain amino acids and total and free tryptophan were determined. Branched chain amino acids decreased from 463 - 108.3 to 364 - 98.9 mol/L (p < 0.03). Free tryptophan increases from 9.2 to 16.3 mol/L (p < 0.006). Furthermore the ratio of free trytophan to branched chain amino acids increased from 2.07 - 0.48 to 4.24 - 0.79 (p < 0.001). This increases the rate of transport of tryptophan accross the blood-brain barrier and also increases the rate of synthesis of 5-hydroxytryptamine in the central nervous system. A high presence of 5-hydroxytryptamine in the brain develops physical and mental fatigue during the triathlon. This data support the participation of amino acids in fatigue process during triathlon

Platelet serotonin content and free and total plasma tryptophan in healthy volunteers during 24 hours

The determination of platelet serotonin (5-HT) and plasma tryptophan concentrations is useful in the diagnosis, investigation of etiologies, and treatment of psychiatric disorders. To determine the usual circadian variations in platelet 5-HT and free and total tryptophan concentrations, we measured these variables during 24 h at 1-h intervals and every 30 min from 2000 to 0800 in seven clinically healthy young men with an HPLC method. No common circadian rhythm for platelet serotonin concentrations was observed in our subjects; however, there was a distinct rhythm for both free and total plasma tryptophan: Concentrations were maximal in the afternoon and minimal during the night.

Relevance of platelet serotonin and plasma tryptophan concentration in normal pregnant women and newborns to early child psychiatry.

Dysfunctions of the serotonergic system are implicated in psychiatric disorders, and there is evidence that a familial element may be significant in childhood autism. The concentrations of platelet 5-HT and free and total plasma tryptophan were determined in healthy pregnant women at each month of pregnancy and, at delivery, in both maternal and umbilical cord blood. A significant rise in the level of platelet 5-HT occured during month 3 and 4 followed by a retum to normal from month 5 until the delivery. The level of total plasma tryptophan remained equal to that in normal healthy non pregnant women until the 6th month. By month 7, it had decreased significantly and remained low until the month 9. At delivery the level fell significantly by -41%. The concentration of free tryptophan varied widely from one month to another but there was a trend towards a progressive increase from month 1 to 9, and at delivery the level returned to basal values. The concentration of 5-HT in the umbilical cord blood was about half that of the maternal blood. Inversely the concentrations of both free and total plasma tryptophan in the umbilical cord blood were nearly twice that of the maternal blood.

Tryptophan Intake Influences Infants’ Sleep Latency

Formula-fed infants have depressed plasma tryptophan concentration relative to human milk-fed infants. Because tryptophan alters sleep-waking patterns in adults, a study was designed to determine whether additional dietary tryptophan could elevate plasma tryptophan concentrations of formula-fed infants to concentrations characteristic of human milk feeding and whether differences in plasma tryptophan or the ratio of plasma tryptophan to the sum of the other plasma large neutral amino acids (tryptophan:LNAA) were of behavioral significance. Infants were fed a formula (13 g protein/L; whey:casein, 34:66) containing either 0, 294, 588 or 882 µmol/L of added tryptophan. Infants fed human milk or commercial formula (15 g protein/L; whey:casein, 18:82) were included for comparison. In formula-fed groups, plasma tryptophan was directly related to tryptophan intake (r = 0.46, P < 0.0005). Infants fed commercial formula or the formula without added tryptophan had lower (P < 0.001) plasma tryptophan compared with infants fed human milk. Only the infants fed the highest tryptophan formula had significantly higher plasma tryptophan:LNAA ratios than the other experimental groups, and these ratios were similar to those of infants fed human milk. The plasma tryptophan:LNAA ratios, not plasma tryptophan concentrations, were predictive of differences in the infants’ sleep latency; infants fed formula containing the highest tryptophan had sleep latencies of 18.7 min, significantly shorter (P < 0.05) than those of infants fed formulas containing less added tryptophan (27.7 min). Feeding infants formulas differing in tryptophan concentration produced differences in sleep latency, which could influence neurobehavioral development. This result was obtained with variations in the level of tryptophan within the range found in commercially available formulas.

Is Postoperative Delirium Related to Reduced Plasma Tryptophan?

The cause of postoperative delirium is unknown. In 7 patients with postcardiotomy delirium (6 men, 1 woman; mean age 67 years), we observed a plasma concentration of tryptophan and a plasma tryptophan ratio significantly lower than in 8 non-delirious postoperative control patients. We suggest that the mental symptoms of postcardiotomy delirium are the consequence of a reduced cerebral tryptophan availability due to a catabolic state.

Hypothalamic neurotransmitter concentrations and meat quality in stressed pigs offered excess dietary tryptophan and tyrosine.

Pale, soft, exudative (PSE) pork occurs, for the most part, from environmental stress on the pig. Amino acid intake may be related to stress susceptibility through hormone and neurotransmitter induction. Two experiments were conducted to determine whether supplementation of 5 g of tryptophan (TRP) or 10 g of tyrosine (TYR) per kilogram of a 14% CP diet would alter the response of pigs to stress as measured by hypothalamic neurotransmitter concentrations and incidence of PSE. Twenty-four (Exp. 1) and 36 (Exp. 2) 92-kg pigs were offered one of three diets: control, TRP-, or TYR-supplemented for 5 d before slaughter. Dietary TRP or TYR supplementation in Exp. 1. doubled (P less than .05) plasma TRP and TYR concentrations, respectively, and increased (P less than .05) 5-hydroxytryptamine, dihydroxyphenyl ethylamine, dihydroxyphenyl acetic acid, and homovanillic acid concentrations in the hypothalamus. Pigs that exhibited stress at slaughter had lower (P less than .05) hypothalamic concentrations of epinephrine, norepinephrine, and 5-hydroxytryptamine. In Exp. 2, pigs were trucked 55 km to a commercial meat packing facility and slaughtered without a rest period. This handling procedure was designed to invoke a high incidence of PSE pork and thus be a strong test of treatments. Supplemental dietary amino acids seemed to alter the frequency distribution of the severity of PSE pork. These data indicate that dietary manipulation of amino acid precursors of neurotransmitters may offer a practical means of reducing stress response in swine.

Tryptophan Fortification of Adapted Formula Increases Plasma Tryptophan Concentrations to Levels Not Different from Those Found in Breast‐Fed Infants

Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula‐fed than in breast‐fed infants. We have measured preprandial plasma amino acid concentrations in infants breast‐fed or fed a formula with a protein concentration of 1–57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast‐fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast‐fed group than in both formula‐fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast‐fed group than in the group fed the tryptophan‐unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast‐fed group versus the group fed the tryptophan‐fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast‐fed infants. The data also confirm that a formula with reduced protein concentration will support normal growth and will produce a plasma amino acid profile not much different from that of a conventional type of formula.

Route of Administration of Tryptophan and Tyrosine Affects Short-Term Food Intake and Plasma and Brain Amino Acid Concentrations in Rats ,

The effects of route of administration of tryptophan and tyrosine on food intake and diet selection and on plasma and brain tryptophan or tyrosine concentrations were studied. Tryptophan and tyrosine given intraperitoneally at 100 mg/kg body wt suppressed food intake by 33–45% over a 2-h feeding period beginning 30 min after injections. No preferential effect was shown for either the high carbohydrate or high protein diet choice. When given intragastrically at this dose, neither tryptophan nor tyrosine affected food intake. Tryptophan, but not tyrosine, at 200, 400 and 600 mg/kg body wt given intragastrically reduced food intake and carbohydrate diet intake by an average of 20 and 25%, respectively, in the first 2 h of feeding. Plasma and brain tryptophan were higher for 30 min following intraperitoneal tryptophan injections than after tryptophan given intragastrically at 100 mg/kg body wt. However, intraperitoneal tyrosine (100 mg/kg body wt) resulted in higher plasma tyrosine levels at 5–10 min but lower levels at 30 min than when tyrosine was given intragastrically. Brain tyrosine was higher after intraperitoneal treatment only at 10 min and was similar to intragastric treatment at other times. When these amino acids were given intragastrically at 400 mg/kg body wt, higher plasma tryptophan, plasma tyrosine and brain tyrosine were found than following intraperitoneal injection of the behaviorally effective dose (100 mg/kg body wt) at 30 min. Thus the reduced effect on food intake of tryptophan or tyrosine given intragastrically compared with intraperitoneally is not readily explained by their lower concentrations in plasma and brain preceding and at the time that the rats had access to food.

Renal Transport of Endogenous Amino Acids

In the late neonatal period of male Wistar rats (10 days old) concentrations in plasma were higher for 5 of 24 amino acids compared to adult animals (2 months old): β-alanine, tyrosine, glycine, histidine, and the dipeptide anserine. The plasma concentrations of tryptophan, valine and leucine were lower in young than in adult rats. The renal clearances of amino acids were lower in young rats, both in relation to 1 g b.w. and related to 1 g kidney weight. In the latter case the differences became more distinct because the relative kidney weight was higher in young than in adult animals (1.17 ± 0.07 vs. 0.82 ± 0.03 g/l00 g b.w.) and significant age differences in renal water content did not exist. The apparently more effective tubular reabsorption capacity in young rats can be explained as follows: Because of the significantly lower GFR in 10-day-old rats compared with adults (0.46 ± 0.03 vs. 1.10 ± 0.09 ml/ min/1 g kidney), the glomerularly filtered load of amino acids is generally lower in young rats (exceptions: tyrosine glycine). Therefore, the amino acid transporting carrier systems are able to reabsorb the absolutely lower amounts of amino acids from the ultrafiltrate in immature animals. This hypothesis is supported if one relates the renal amino acid clearance to the clearance of inulin. In this way it is possible to show that there are absolutely no differences between both age groups indicating mature transport systems for endogenous amino acids as early as in 10-day-old rats. The urinary excretion of amino acids in young and adult animals was less than 1-5% of the filtered load and age differences were not significant.

Amino acids and serotonin in Limax maximus after a tryptophan devoid diet

1. 1. Animals avoid diets lacking an essential amino acid, such as tryptophan (TRP), the precursor for serotonin (5-HT). 5-HT is important in the control of feeding. 2. 2. To study the effects of TRP deprivation, slugs were fed TRP-devoid (DEV) or control (COR) diets. 3. 3. Food intake was depressed in DEV, as expected, but after 2 weeks, the serontonergic metacerebral giant cell in DEV was still functional. 4. 4. Neither brain 5-HT nor plasma TRP concentration was affected. 5. 5. Compared with food-restricted animals that had reductions in most amino acids, the DEV group sustained a marked plasma amino acid imbalance.

Physical and mental fatigue: metabolic mechanisms and importance of plasma amino acids.

There are at least 5 metabolic causes of fatigue, a decrease in the phosphocreatine level in muscle, proton accumulation in muscle, depletion of the glycogen store in muscle, hypoglycaemia and an increase in the plasma concentration ratio of free tryptophan/branched-chain amino acids. Proton accumulation may be a common cause of fatigue in most forms of exercise and may be an important factor in fatigue in those persons who are chronically physically inactive and also in the elderly: thus, the aerobic capacity markedly decreases under these conditions, so that ATP must be synthesized by the much less efficient anaerobic system. A marked increase in the plasma fatty acid level, which may occur when liver glycogen store is depleted and when hypoglycaemia results, or during intermittent exercise when the rate of fatty acid oxidation may not match the mobilisation of fatty acids, could be involved indirectly in fatigue. This is because such an increase in the plasma level of fatty acids raises the free plasma concentration of tryptophan, which can increase the entry of tryptophan into the brain, which will increase the brain level of 5-hydroxytryptamine: there is evidence that the latter may be involved in central fatigue. In this case, provision of branched-chain amino acids in order to maintain the resting plasma concentration ratio of free tryptophan/branched-chain amino acids should delay fatigue--there is prima facie evidence in support of this hypothesis. This hypothesis may have considerable clinical importance.

Circadian variation in total plasma tryptophan. Antidepressant treatment: Drugs and phase advance

The authors investigated hourly total plasma tryptophan concentrations over a 24 hour period in 3 patients with bipolar depression during 2 types of treatment: a phase advance process and conventional antidepressant therapy. Both treatment modalities increased the 24 hour mean tryptophan levels and the amplitude of circadian tryptophan concentrations. By contrast, in a previous study, moderately decreased tryptophan levels and a blunted amplitude in the circadian rhythm were observed in these same patients in a depressive phase.

Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease.

Some children with coeliac disease show behavioural disorders such as depression and other signs which have been correlated with reduced central monoamine metabolism. We have therefore investigated the brain availability of the monoamine precursors tryptophan and tyrosine in 15 untreated children with coeliac disease and 12 treated children with coeliac disease as well as in 12 control children. Significantly decreased plasma concentrations of tryptophan were found in untreated children (mean (SD) 13 (4) mumols/l, p less than 0.001) compared with treated children (31 (13) mumols/l), and in both groups of coeliac children when compared with control children (81 (22) mumols/l). A significantly lower ratio of plasma tryptophan to large neutral amino acids (tyrosine, valine, isoleucine, leucine, and phenylalanine) was also observed, which could indicate impaired brain availability of tryptophan in coeliac children and was more pronounced in untreated children. The impaired availability of tryptophan could produce decreased central serotonin synthesis and in turn behaviour disorders in children with coeliac disease.

Is postoperative delirium related to reduced plasma tryptophan?

The cause of postoperative delirium is unknown. In 7 patients with postcardiotomy delirium (6 men, 1 woman; mean age 67 years), we observed a plasma concentration of tryptophan and a plasma tryptophan ratio significantly lower than in 8 non-delirious postoperative control patients. We suggest that the mental symptoms of postcardiotomy delirium are the consequence of a reduced cerebral tryptophan availability due to a catabolic state.

Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period.

Concentrations of tryptophan (free and protein bound) and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.

Serotonin Synthesis Rate Measured in Living Dog Brain by Positron Emission Tomography

In vivo measurements by positron emission tomography of the brain serotonin synthesis rates in the normal dog, in the dog with increased plasma tryptophan concentration, and in the dog under different arterial oxygen tensions are described. The method described here permits repeated measurements in the same brain for the first time. An increase in the plasma tryptophan concentration from 16.6 to 191.5 and then to 381 microM resulted in close to a linear increase in the brain serotonin synthesis rate. When PaO2 was raised from 76 +/- 2 to 106 +/- 1 mm Hg, the rate of serotonin synthesis in the dog brain increased from 39 +/- 8 to 54 +/- 10 pmol g-1 min-1. The estimates of the Michaelis-Menten constants, Kappm and Vmax, for the transport of tryptophan through the blood-brain barrier are 303 +/- 54 microM and 63 +/- 10 nmol g-1 min-1, respectively.

Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss

Plasma total tryptophan (TRP) concentration was significantly lower in 31 patients with major depression compared to a healthy control group. The ratio of plasma TRP concentration to that of other branch chain amino acids (the TRP: BCAA ratio) was also decreased. Further analysis revealed that the decrease in plasma TRP and TRP: BCAA ratio was most apparent in patients with major depression and melancholia. Overall, women but not men had significantly decreased plasma tryptophan concentrations, perhaps because of a contributory effect of weight loss; this latter effect, however, could not be distinguished clearly from a diagnosis of melancholia. Our data suggest that in some depressed patients, reductions in plasma tryptophan availability may contribute to abnormalities in brain 5-hydroxytryptamine function.

Effect of Tryptophan and Cyproheptadine on Food Intake

Whether tryptophan in the usual dose found in total parenteral nutrition (TPN) solutions caused a decrease in food intake was investigated in 16 adult male Fischer 344 rats. A jugular venous catheter was placed, and patency was maintained with a continuous infusion of normal saline at 3 ml/hr. After a 10-day recovery period, eight normal saline control rats were sacrificed and the remaining eight rats were given a parenteral nutrition solution (PN-50) at 3 ml/hr, providing 50% of the rat's daily energy requirement as 5% dextrose and 2% Intralipid. On day 14, study rats were further divided into two subgroups. Subgroup A received tryptophan (180 mg/day) added to the solution for 5 days. Subgroup B received the serotonin-receptor blocker, cyproheptadine 24 mg/kg/day, continuously for 5 days, and on day 16, tryptophan (0.25% = 180 mg/kg/day) was added to the solution for 3 days. Chow and water was continuously available and spontaneous food intake was measured daily. Study rats were sacrificed on day 19. Plasma amino acids and insulin and whole brain biogenic amines were compared with those in control rats using Student's t-test. With administration of PN-50, spontaneous food intake decreased to about 60% compared with the pre-PN level. The addition of tryptophan to the continuous infusion of PN-50 did not decrease spontaneous food intake further.(ABSTRACT TRUNCATED AT 250 WORDS)