scholarly journals Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4012
Author(s):  
Iris Scala ◽  
Daniela Concolino ◽  
Anna Nastasi ◽  
Giulia Esposito ◽  
Daniela Crisci ◽  
...  
Keyword(s):  
Amino Acids ◽  
Slow Release ◽  
Good Adherence ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Beneficial Effects ◽  
Adherence To Diet ◽  
Low Protein ◽  
Single Oral Administration ◽  
Stable Plasma

The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load. Fourteen phenylketonuric patients aged ≥13 years were enrolled in a 6-week protocol. Oral acute Phe loads of 250 and 500 mg were added to the evening meal together with srLNAAs (0.5 gr/kg). Phe and tyrosine were dosed before dinner, 2h-after dinner, and after the overnight fast. After oral Phe loads, mean plasma Phe remained stable and below 600 µmol/L. No Phe peaks were registered. Tyrosine levels significantly increased, and Phe/Tyrosine ratio decreased. No adverse events were registered. In conclusion, a single oral administration of srLNAAs at the dose of 0.5 gr/kg is effective in maintaining stable plasma Phe during acute oral loads with Phe-containing food and may be added to the dietetic scheme in situations in which patients with generally good adherence to diet foresee a higher than prescribed Phe intake due to their commitments.

Stimulated amino acid imbalance and histidine transport in rat brain slices

1975 ◽  
Vol 229 (1) ◽  
pp. 229-234 ◽  
Author(s):  
J Lutz ◽  
JK Tews ◽  
AE Harper
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brain Slices ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Low Protein ◽  
Amino Acid Imbalance ◽  
The Brain

Histidine concentration in the brain decreases rapidly when rats are fed a low protein diet in which an amino acid imbalance is created by addition of an amino acid mixture devoid of histidine. Competition for histidine transport into the brain was suggested as an explanation for this effect. Therefore, animo acid mixtures simulating composition of plasma from rats fed basal or histidine-imbalanced diets were added to media to evaluate their effects on uptake of histidine by brain slices during a 60-min incubation period. At the concentrations actually found in plasma, the unbalanced mixture decreased histidine uptake significantly more than did the basal mixture. Two distinct inhibition patterns were observed with different groups of amino acids: a linear decrease in histidine uptake with a mixture of the small neutral, hydroxyl, basic, and acidic amino acids, and a hyperbolic decrease with a mixture of large neutral amino acids, and a hyperbolic decrease with a mixture of large neutral amino acids. Inhibition of histidine transport by the complete mixtures reflected these two effects. Plasma patterns and concentrations of competitive amino acids as well as the concentration of histidine appear to be factors involved in decreasing histidine transport into the brain.

scholarly journals The Impact of a Slow-Release Large Neutral Amino Acids Supplement on Treatment Adherence in Adult Patients with Phenylketonuria

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2078 ◽  
Author(s):  
Alessandro P. Burlina ◽  
Chiara Cazzorla ◽  
Pamela Massa ◽  
Christian Loro ◽  
Daniela Gueraldi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Amino Acids ◽  
Medication Adherence ◽  
Slow Release ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Adherence To Medication ◽  
Full Adherence ◽  
Adherence To Therapy

The gold standard treatment for phenylketonuria (PKU) is a lifelong low-phenylalanine (Phe) diet supplemented with Phe-free protein substitutes. Adherence to therapy becomes difficult after childhood. Supplementing with large neutral amino acids (LNAAs) has been proposed as an alternative medication to Phe-free protein substitutes (i.e., amino acid mixtures). The aim of this study was to evaluate adherence to therapy and quality of life (QoL) in a cohort of sub-optimally controlled adult PKU patients treated with a new LNAA formulation. Twelve patients were enrolled in a 12-month-trial of slow-release LNAAs (1g/kg/day) plus a Phe-restricted diet. Medication adherence was measured with the Morisky Green Levine Medication Adherence Scale; the QoL was measured using the phenylketonuria-quality of life (PKU-QoL) questionnaire. Phe, tyrosine (Tyr) levels, and Phe/Tyr ratios were measured fortnightly. Before treatment, 3/12 patients self-reported a ‘medium’ adherence to medication and 9/12 reported a low adherence; 60% of patients reported a full adherence over the past four weeks. After 12 months of LNAA treatment, all patients self-reported a high adherence to medication, with 96% reporting a full adherence. Phe levels remained unchanged, while Tyr levels increased in most patients. The Phy/Tyr ratio decreased. All patients had a significant improvement in the QoL. LNAAs may give patients a further opportunity to improve medication adherence and, consequently, their QoL.

Atypical amino acids inhibit histidine, valine, or lysine transport into rat brain

1983 ◽  
Vol 245 (4) ◽  
pp. R556-R563 ◽  
Author(s):  
J. K. Tews ◽  
A. E. Harper
Keyword(s):  
Amino Acids ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
Brain Slices ◽  
Aromatic Amino Acids ◽  
Brain Barrier ◽  
Basic Amino Acids ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Single Meal

Transport of histidine, valine, or lysine into rat brain slices and across the blood-brain barrier (BBB) was determined in the presence of atypical nonprotein amino acids. Competitors of histidine and valine transport in slices were large neutral amino acids including norleucine, norvaline, alpha-aminooctanoate, beta-methylphenylalanine, and alpha-aminophenylacetate. Less effective were aromatic amino acids with ring substituents; ineffective were basic amino acids and omega-amino isomers of norleucine and aminooctanoate. Lysine transport was moderately depressed by homoarginine or ornithine plus arginine; large neutral amino acids were also similarly inhibitory. Histidine or valine transport across the BBB was also strongly inhibited by large neutral amino acids that were the most effective competitors in the slices (norvaline, norleucine, alpha-aminooctanoate, and alpha-aminophenylacetate); homoarginine and 8-aminooctanoate were ineffective. Homoarginine, ornithine, and arginine almost completely blocked lysine transport, but the large neutral amino acids were barely inhibitory. When rats were fed a single meal containing individual atypical large neutral amino acids or homoarginine, brain pools of certain large neutral amino acids or of arginine and lysine, respectively, were depleted.

scholarly journals Large Neutral Amino Acids (LNAAs) Supplementation Improves Neuropsychological Performances in Adult Patients with Phenylketonuria

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1092 ◽  
Author(s):  
Iris Scala ◽  
Maria Pia Riccio ◽  
Maria Marino ◽  
Carmela Bravaccio ◽  
Giancarlo Parenti ◽  
...  
Keyword(s):  
Amino Acids ◽  
Executive Functions ◽  
Metabolic Control ◽  
Cognitive Functions ◽  
Well Being ◽  
Wisconsin Card Sorting Test ◽  
Card Sorting ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Poor Metabolic Control

Phenylketonuria is an inborn error of phenylalanine (Phe) metabolism diagnosed by newborn screening and treated early with diet. Although diet prevents intellectual disability, patients often show impairment of executive functions, working memory, sustained attention, and cognitive flexibility. Large neutral amino acids (LNAAs) have been proposed as a dietary supplement for PKU adults. Few studies show that LNAAs may help in improving metabolic control as well as cognitive functions. In this study, 10 adult PKU patients with poor metabolic control were treated for 12 months with LNAAs (MovisCom, 0.8–1 g/kg/day) and underwent Phe and Tyrosine (Tyr) monitoring monthly. Neuropsychological assessment was performed at T0, T+3, and T+12 months by using the American Psychological General Well-Being Index, the Wisconsin Card Sorting Test, the Test of Attentional Performance, and the 9-Hole Peg Test. No change in plasma Phe levels was observed during LNAAs supplementation, while Tyr levels significantly improved during LNAAs supplementation (p = 0.03). Psychometric tests showed an improvement of distress and well-being rates, of executive functions, attention, and vigilance, whereas no difference was noted regarding hand dexterity. This study adds evidence of the advantage of LNAAs supplementation in improving cognitive functions and well-being in patients with PKU with poor metabolic control.

scholarly journals Trans-placental Gradients of Large Neutral Amino Acids (LNAA) in Baboon Pregnancy With Fasting,Feeding and Tryptophan (TRP) Infusion † 298

1998 ◽  
Vol 43 ◽  
pp. 53-53
Author(s):  
S Rastogi ◽  
K Abildskov ◽  
S S Daniel ◽  
M Garland ◽  
K Schulze ◽  
...  
Keyword(s):  
Amino Acids ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids

Acute effects of aspartame on large neutral amino acids and monoamines in rat brain

Life Sciences ◽  
1983 ◽  
Vol 32 (14) ◽  
pp. 1651-1658 ◽  
Author(s):  
John D. Fernstrom ◽  
Madelyn H. Fernstrom ◽  
Marcia A. Gillis
Keyword(s):  
Amino Acids ◽  
Rat Brain ◽  
Acute Effects ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids

Large neutral amino acids in the treatment of phenylketonuria (PKU)

2006 ◽  
Vol 29 (6) ◽  
pp. 732-738 ◽  
Author(s):  
R. Matalon ◽  
K. Michals-Matalon ◽  
G. Bhatia ◽  
E. Grechanina ◽  
P. Novikov ◽  
...  
Keyword(s):  
Amino Acids ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids

Lowering Brain Phenylalanine Levels by Giving Other Large Neutral Amino Acids

1976 ◽  
Vol 33 (10) ◽  
pp. 684 ◽  
Author(s):  
Arnold E. Andersen
Keyword(s):  
Amino Acids ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids

scholarly journals Influence of fluctuations of plasma large neutral amino acids with normal diets on the clinical response to levodopa.

1989 ◽  
Vol 52 (4) ◽  
pp. 481-487 ◽  
Author(s):  
J G Nutt ◽  
W R Woodward ◽  
J H Carter ◽  
T L Trotman
Keyword(s):  
Amino Acids ◽  
Clinical Response ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids
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