scholarly journals Dietary Supplementation with Casein Glycomacropeptide, Leucine and Tryptophan Reduces Plasma Amino Acid Levels in Men

2021 ◽  
pp. 1-28
Author(s):  
Erik Roj Larsen ◽  
Anette Juel ◽  
Erik Jensen ◽  
Tristan R. Hollyer ◽  
Gregers Wegener

Abstract Background The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships, and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine, and tyrosine, in plasma, and therefore be a potential new intervention to treat acute manic episodes. Method The study was designed as a double-blind randomised dose-response study of CGMP (with added leucine and tryptophan) in 15 healthy men, receiving 3 different doses of CGMP with an interval of at least 14 days. Results Administration of CGMP produced a dose dependent depletion of plasma aromatic amino acids. The total area under the curve of plasma ratios of phenylalanine-tyrosine compared to the level of leucine-isoleucine-valine-tryptophan was CGMP(20g): 3.648 [SE:0.3281]; CGMP(40g): 2.368 [SE:0.1858]; CGMP(60g)1.887 [SE:0.2591]. A comparison of the groups showed a dose dependent statistical difference, with a One-Way ANOVA summary (Dunnett) F= 11.87, p= 0.0003, CGMP 20g vs CGMP 40g, p= 0.0042, CGMP 20g vs CGMP 60g, p= 0.0002. No significant side effects were observed. Conclusions This study demonstrate CGMP is a well-tolerated and effective mixture, and that 60 g CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). The effect seems to be highest after 3-4 hours. We therefore conclude that this dose should be the one considered for future studies involving CGMP in humans.

2011 ◽  
Vol 105 (4) ◽  
pp. 611-617 ◽  
Author(s):  
E. Siobhan Mitchell ◽  
Marieke Slettenaar ◽  
Frits Quadt ◽  
Timo Giesbrecht ◽  
Joris Kloek ◽  
...  

Serotonin synthesis critically depends on plasma levels of tryptophan (TRP). Earlier studies have shown that for mood and cognitive benefits to occur, the ratio between TRP and other large neutral amino acids (LNAA) has to be increased by approximately 40 %. The present study investigated the dose-dependent effects of a TRP-rich hydrolysed protein (egg-protein hydrolysate, EPH) on the plasma TRP:LNAA. Moreover, it was investigated whether EPH could increase TRP:LNAA in the presence of 2 g of milk protein (MP). In a randomised double-blind crossover design, plasma amino acids were measured every 30 min for 3·5 h after ingestion of a drink containing either three different doses of 4, 8 and 12 g EPH containing 270, 560 or 800 mg of TRP, respectively, the combination of 4 g EPH and 2 g MP (74 mg TRP), or 4 g MP (148 mg TRP) in twenty healthy subjects with a mean age of 52 years. All three EPH doses caused significant increases of TRP:LNAA above 40 % at 30, 60 and 90 min after consumption in a dose-dependent manner. Compared with the 4 g EPH, the increase in TRP:LNAA in the 4 g EPH with 2 g MP condition was significantly lower at 60 min (63 v. 44 %, P < 0·001) and did not differ significantly at 90 min (58 v. 53 %, P>0·05). The present study showed that a low dose of 4 g EPH with even the addition of 2 g MP was sufficient to increase the ratio of TRP:LNAA above 40 %. Thus, EPH offers a viable ingredient to increase TRP availability.


1990 ◽  
Vol 259 (1) ◽  
pp. G78-G85 ◽  
Author(s):  
M. L. Siegle ◽  
H. R. Schmid ◽  
H. J. Ehrlein

In the present study, effects of ileal infusions of nutrients on motor patterns of the proximal small intestine and on gastric emptying were investigated in dogs. An acaloric meal was administered orally, and equicaloric loads of amino acids, oleate, and glucose were infused into the ileum at different doses (0.3, 0.6, and 0.9 kJ/min). The computerized analysis of motor patterns was focused on the differentiation between stationary and propagated contractions recorded by closely spaced extraluminal strain gauges. All three nutrients exerted inhibitory effects on gastric emptying and on contraction force and frequency of the proximal small intestine. Additionally, the propulsive motor pattern induced by the acaloric meal was modulated by reducing the number of contraction waves and their length of spread. All the effects were dose dependent. Among the three nutrients, glucose significantly changed motility at lower doses compared with amino acids and oleate. We conclude that in dogs the ileal brake mechanism is induced by all three nutrients and that it influences not only contraction force and frequency but also the motor patterns of the proximal small intestine.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Filip Ottosson ◽  
Ulrika Ericson ◽  
Peter Almgren ◽  
Jeanette Nilsson ◽  
Martin Magnusson ◽  
...  

High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia.


1998 ◽  
Vol 9 (suppl e) ◽  
pp. 16E-22E
Author(s):  
Jerome J Schentag

OBJECTIVE: To characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis (ABECB), with particular attention to the speed of bacterial killing. This was possible because the study design incorporated daily cultures of the patients’ sputum.PATIENTS AND METHODS: The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age who were part of a multicentre, randomized, double-blind, dose-response study. Patients were randomly assigned to receive oral regimens of grepafloxacin - 200, 400 or 600 mg - each administered once daily for 14 days. Daily cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the days to eradication of each strain of bacteria. Grepafloxacin plasma concentration profiles were best fit by a pharmacokinetic model with first order absorption following a lag time between administration of the dose and onset of systemic absorption. Pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure and probability of clinical cure, and time to eradication.RESULTS: All three measures of response were strongly related to the 24 h area under the inhibitory curve (AUIC) (area under the curve/minimum inhibitory concentration). At an AUIC below of 75/serum inhibiting titre (SIT) x 24 h, the percentage probability of clinical cure was 71 %; at an AUIC between 75 and 175, it was 80% (P<0.05); and, at an AUTC above 175, it was 98% (P<0.01).CONCLUSION: The speed of bacterial killing for grepafloxacin in ABECB patients was highly related to AUIC; values below 75 appear inadequate, and values greater than 175 were optimal.


1981 ◽  
Vol 60 (1) ◽  
pp. 95-100 ◽  
Author(s):  
S. Eriksson ◽  
L. Hagenfeldt ◽  
J. Wahren

1., Intravenous infusions of l-valine (600 μmol/min), l-isoleucine (150 μmol/min), l-leucine (300 μmol/min) and a mixture of the three branched-chain amino acids (70% l-leucine, 20% l-valine, 10% l-isoleucine; 270 μmol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P < 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.


2002 ◽  
Vol 283 (4) ◽  
pp. E648-E657 ◽  
Author(s):  
Elisabet Børsheim ◽  
Kevin D. Tipton ◽  
Steven E. Wolf ◽  
Robert R. Wolfe

This study tests the hypothesis that a dose of 6 g of orally administered essential amino acids (EAAs) stimulates net muscle protein balance in healthy volunteers when consumed 1 and 2 h after resistance exercise. Subjects received a primed constant infusion ofl-[2H5]phenylalanine andl-[1-13C]leucine. Samples from femoral artery and vein and biopsies from vastus lateralis were obtained. Arterial EAA concentrations increased severalfold after drinks. Net muscle protein balance (NB) increased proportionally more than arterial AA concentrations in response to drinks, and it returned rapidly to basal values when AA concentrations decreased. Area under the curve for net phenylalanine uptake above basal value was similar for the first hour after each drink (67 ± 17 vs. 77 ± 20 mg/leg, respectively). Because the NB response was double the response to two doses of a mixture of 3 g of EAA + 3 g of nonessential AA (NEAA) (14), we conclude that NEAA are not necessary for stimulation of NB and that there is a dose-dependent effect of EAA ingestion on muscle protein synthesis.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1017 ◽  
Author(s):  
Cassandra Sparkes ◽  
Andrew J. Sinclair ◽  
Robert A. Gibson ◽  
Paul L. Else ◽  
Barbara J. Meyer

(1) Aim: the aim of this secondary analysis was to report the variability in response to n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation in erythrocytes, plasma and whole blood of a previously published dose response study. (2) Methods: a randomized, double-blind, placebo-controlled trial of parallel design was conducted, whereby pre-menopausal women were randomly assigned to consume 0, 0.35, 0.7 or 1 g/day of supplemental eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Fasted blood samples were taken at baseline and after eight weeks intervention. Erythrocyte, plasma and whole blood fatty acids were extracted using the method of Lepage and Roy and analysed using gas chromatography. (3) Results: There were significant increases in EPA plus DHA levels in the 0.7 g and 1 g dose groups, with the highest increase with the 1 g dose notably: in erythrocytes (from 5.69% to 7.59%), plasma (from 2.94% to 5.48%) and in whole blood (from 3.81% to 6.03%). There was high variability in response to the supplement in erythrocytes, plasma and whole blood across the different doses. (4) Conclusion: there is high individual variability in n-3 LCPUFA levels in response to n-3 LCPUFA supplementation, which should be taken into account in clinical trials using n-3 LCPUFA supplements.


2000 ◽  
Vol 23 (6) ◽  
pp. 375-388 ◽  
Author(s):  
J. Steczko ◽  
K.C. Bax ◽  
S.R. Ash

Changes in plasma amino acid concentrations were measured in patients with hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis Unit, “the Unit”) or hemodiabsorption plus sorbent-based pheresis treatment (using the Liver Dialysis Plasmafilter Unit, “the PF-Unit”) Systems. Eight patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin and/or creatinine levels and respiratory or renal failure were treated for 1–3 days with the Unit alone. Three of these were also treated with the Unit containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic failure treated with the PF Unit also had 10 g of branched chain amino acid (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post-plasma samples were drawn and high performance liquid chromatography (HPLC) was used to separate and detect amino acids in the plasma. Both the Unit and the PF-Unit have the capability to selectively remove various amino acids, especially aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and isolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and PF-Unit patients was 1.43 (±0.58). Treatments by both systems resulted in an increase of BCAA levels in blood and concomitant decrease of AAA levels, with an average Fischer ratio improvement of 30–38% for the Unit and PF-Unit without BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels of many other amino acids (such as alanine, glycine, proline or lysine) increased during both Unit and PF-Unit treatments. The removal of strongly protein-bound toxin and amino acids such as tryptophan and sulphydryl amino acids was more effective by the PF-Unit. Both the Unit and the PF-Unit have the unique capability to remove toxic aromatic amino acids while increasing BCAA levels in patient. The increase in many amino acid levels may be related to the removal of toxins that interfere with normal amino acid metabolism. The addition of the PF module improves the removal of bilirubin and similarly protein-bound chemicals. Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with other extracorporeal devices.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Karin Linnewiel Hermoni ◽  
Yoav Sharoni

Abstract Objectives Examine the effect of a carotenoid-rich Tomato Nutrient Complex on blood pressure and perform a dose-response analysis and uncover the optimal effective supplementation dose in maintaining blood pressure within normal range among individuals with systolic blood pressure between 130–140 mmHg, otherwise healthy subjects. Methods In this double-blind, randomized, placebo-controlled study, different doses of the Tomato Nutrient Complex were examined, corresponding to 5 mg, 15 mg, and 30 mg lycopene. The effect of the tomato-derived treatment was compared with 15 mg of synthetic Lycopene and placebo over 8 weeks of treatment. In addition, we analyzed the bioavailability of the carotenoids following treatment with different doses of the Tomato Nutrient Complex in a group of 25 healthy volunteers. Volunteers were treated for four weeks with Tomato Nutrient Complex providing 2, 5 and 15 mg lycopene. Results Results indicate that treatment for 8 weeks with Tomato Nutrient Complex standardized to contain 15 mg or 30 mg of lycopene was associated with statistically significant reductions in mean SBP of 9.7 mmHg and 7 mmHg compared to baseline values respectively. Treatment with the lower dose Tomato Nutrient Complex standardized for 5 mg of lycopene, or treatment with 15 mg of synthetic lycopene as a standalone did not show a significant effect. In parallel, we analyzed the bioavailability of the carotenoids in healthy subjects. In a group of 25 healthy volunteers treated for 4 weeks with different doses of the Tomato Nutrient Complex. we identified a dose dependent and significant increase in blood level of lycopene, phytoene, and phytofluene. Conclusions Overall, the results suggest that the carotenoids in the Tomato Nutrient Complex are well absorbed in a dose dependent manner and that only the carotenoid levels achieved by the dose corresponding to 15 mg lycopene or more, is correlated to a beneficial effect on systolic blood pressure while lower doses and standalone lycopene are not enough to drive the effect. Funding Sources Lycored.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 950 ◽  
Author(s):  
Talia Wolak ◽  
Yoav Sharoni ◽  
Joseph Levy ◽  
Karin Linnewiel-Hermoni ◽  
David Stepensky ◽  
...  

Oxidative stress is implicated in the pathogenesis of essential hypertension, a risk factor for cardiovascular morbidity and mortality. Tomato carotenoids such as lycopene and the colorless carotenoids phytoene and phytofluene induce the antioxidant defense mechanism. This double-blind, randomized, placebo-controlled study aimed to find effective doses of Tomato Nutrient Complex (TNC) to maintain normal blood pressure in untreated hypertensive individuals. The effect of TNC treatment (5, 15 and 30 mg lycopene) was compared with 15 mg of synthetic lycopene and a placebo over eight weeks. Results indicate that only TNC treatment standardized for 15 or 30 mg of lycopene was associated with significant reductions in mean systolic blood pressure (SBP). Treatment with the lower dose standardized for 5 mg of lycopene or treatment with 15 mg of synthetic lycopene as a standalone had no significant effect. To test carotenoid bioavailability, volunteers were treated for four weeks with TNC providing 2, 5 or 15 mg lycopene. The increase in blood levels of lycopene, phytoene, and phytofluene was dose dependent. Results suggest that only carotenoid levels achieved by the TNC dose of 15 mg lycopene or higher correlate to a beneficial effect on SBP in hypertensive subjects while lower doses and lycopene alone do not.


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