scholarly journals Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1976
Author(s):  
Naoki Miura ◽  
Hideki Matsumoto ◽  
Luc Cynober ◽  
Patrick J. Stover ◽  
Rajavel Elango ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Adult Males ◽  
Self Assessment ◽  
Oral Supplementation ◽  
Safe Level ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Plasma Tyrosine

Phenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalanine and oral serine. Healthy male adults (n = 60, 38.2 ± 1.8y) completed graded dosages of either phenylalanine or serine supplement (3, 6, 9 and 12 g/d) for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality and mental self-assessment. At low dosages, minor changes in serum electrolytes and plasma non-essential amino acids glutamine and aspartic acid concentrations were observed. Serine increased its plasma concentrations at high supplemental dosages (9 and 12 g/day), and phenylalanine increased plasma tyrosine concentrations at 12 g/day, but those changes were not considered toxicologically relevant. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of phenylalanine or serine without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of phenylalanine and serine supplementation in healthy adult males was determined to be 12 g/day.

scholarly journals Progress towards reduced-crude protein diets for broiler chickens and sustainable chicken-meat production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sonia Yun Liu ◽  
Shemil P. Macelline ◽  
Peter V. Chrystal ◽  
Peter H. Selle
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Broiler Chickens ◽  
Crude Protein ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Chicken Meat ◽  
Meat Production ◽  
Accurate Identification ◽  
Reduced Crude Protein

AbstractThe prime purpose of this review is to explore the pathways whereby progress towards reduced-crude protein (CP) diets and sustainable chicken-meat production may be best achieved. Reduced-CP broiler diets have the potential to attenuate environmental pollution from nitrogen and ammonia emissions; moreover, they have the capacity to diminish the global chicken-meat industry’s dependence on soybean meal to tangible extents. The variable impacts of reduced-CP broiler diets on apparent amino acid digestibility coefficients are addressed. The more accurate identification of amino acid requirements for broiler chickens offered reduced-CP diets is essential as this would diminish amino acid imbalances and the deamination of surplus amino acids. Deamination of amino acids increases the synthesis and excretion of uric acid for which there is a requirement for glycine, this emphasises the value of so-called “non-essential” amino acids. Starch digestive dynamics and their possible impact of glucose on pancreatic secretions of insulin are discussed, although the functions of insulin in avian species require clarification. Maize is probably a superior feed grain to wheat as the basis of reduced-CP diets; if so, the identification of the underlying reasons for this difference should be instructive. Moderating increases in starch concentrations and condensing dietary starch:protein ratios in reduced-CP diets may prove to be advantageous as expanding ratios appear to be aligned to inferior broiler performance. Threonine is specifically examined because elevated free threonine plasma concentrations in birds offered reduced-CP diets may be indicative of compromised performance. If progress in these directions can be realised, then the prospects of reduced-CP diets contributing to sustainable chicken-meat production are promising.

Effect of Aging on Free Amino Acids and Electrolytes in Leg Skeletal Muscle

1979 ◽  
Vol 56 (5) ◽  
pp. 427-432 ◽  
Author(s):  
P. Möller ◽  
J. Bergström ◽  
S. Eriksson ◽  
P. Fürst ◽  
K. Hellström
Keyword(s):  
Amino Acids ◽  
Free Amino Acids ◽  
Free Amino ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
The Elderly ◽  
Essential Amino Acids ◽  
Elderly Men ◽  
Healthy Elderly ◽  
The Difference

1. The concentrations of electrolytes and free amino acids in plasma and the quadriceps femoris muscle were studied in ten apparently healthy elderly men, 52–77 years of age. The results were compared with those previously recorded for men 20–36 years old. 2. The two groups of subjects did not differ with regard to serum electrolytes and intracellular water content but the extracellular water in the older subjects exceeded that of the younger group by about 50%. The muscle specimens of the elderly men were also characterized by a 40% elevation of their total contents of Na+ and Cl−, whereas the content of K+ and Mg2+ was almost identical in both groups. 3. The means recorded for the plasma concentrations of most amino acids tended to be higher in the elderly men. The differences reached statistical significance for tyrosine, histidine, valine, lysine and total essential amino acids. In keeping with the findings in plasma, the amino acid concentrations in the muscle of the older group tended to exceed those of the younger ones. The difference reached statistical significance with regard to total amino acids, essential and non-essential amino acids, aspartate, alanine, citrulline, histidine, arginine, leucine and lysine. The various mechanisms that may contribute to these findings are discussed.

Effect of diet and infusion of volatile fatty acids into the rumen on the concentration of plasma free amino acids in sheep

1982 ◽  
Vol 48 (3) ◽  
pp. 519-526 ◽  
Author(s):  
J. R. Mercer ◽  
E. L. Miller
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Free Amino ◽  
Volatile Fatty Acids ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Protein Nitrogen ◽  
Post Infusion ◽  
Limiting Amino Acid ◽  
The Mean

1. The effect of supplementing barley diets with urea (U), extracted decorticated groundnut meal (GNM) or Peruvian fish meal (PFM) on plasma free amino acid concentrations in sheep have been examined and the first limiting amino acid has been indicated by measuring the changes in the concentration of the plasma essential amino acids (PEAA) during a rumen infusion of a volatile fatty acid (VFA) mixture.2. Three wethers fitted with rumen and re-entrant duodenal cannulas were given isonitrogenous, isoenergetic diets containing (g/kg dry matter (DM)) U 20, GNM 106 or PFM 78, the crude protein (nitrogen × 6.25) contents being 139, 145 and 148 respectively. The sheep were fed hourly, the mean daily dm intake being 0.634 kg.3. Plasma concentrations of valine, threonine, lysine, isoleucine and leucine were linearly related to their concentrations in duodenal digesta.4. A VFA mixture was infused into the rumen for 6 h to supply (mmol/min) acetate 1.47, propionate 0.22 and n-butyrate 0.27. Blood samples were taken 6 h before, during and 12 h after the end of the infusion.5. The concentration of all PEAA decreased relative to the pre-infusion and post-infusion controls but there were no significant differences between diets.6. The mean decreases in concentration averaged over all three diets showed that the decrease in concentration of methionine (41.5%) was far greater than for any other essential amino acid suggesting that under these conditions methionine was the first limiting amino acid.

scholarly journals Response of adult rats to deficiencies of different essential amino acids

1974 ◽  
Vol 31 (1) ◽  
pp. 47-57 ◽  
Author(s):  
A. K. Said ◽  
D. M. Hegsted ◽  
K. C. Hayes
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nutritive Value ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
The Body ◽  
Adult Rats ◽  
Short Period ◽  
Body Weights ◽  
Fatty Livers

1. Adult rats were fed on diets free of either lysine, methionine, threonine or protein. The threonine- and protein-deficient animals lost weight at approximately the same rate, about 100 g in 14 weeks, at which time several were moribund. In contrast, lysine-deficient animals lost only about 30 g in 14 weeks and had lost only 46 g after 22 weeks, when they were killed. Methionine-deficient animals showed an intermediate response. Losses in weight of several tissues – kidney, heart and two muscles – were related to, but not necessarily proportional to, the loss of body-weight. Liver weights relative to body-weights were large in lysine- and threonine-deficient animals and smallest in methionine-deficient animals.2. Adult rats were fed on diets containing zero, a moderate amount (about twice the estimated minimal requirement) or an excess (about four times the estimated requirement) of lysine or threonine in all combinations (3 × 3 design). Analysis of variance of the body-weights, tissue weights and tissue nitrogen contents indicated, in general, a significant effect of each amino acid, as expected, but also, in most instances, a significant interaction. Plasma concentrations of lysine and threonine were affected by the intakes of the respective amino acids, but plasma lysine concentrations were also affected by the threonine intake.3. Liver histology also suggested significant interactions between the two amino acids. Animals given no lysine but moderate amounts of threonine developed severely fatty livers; next most severely affected were animals receiving excess of both amino acids. Threonine deficiency, in the presence or absence of lysine, produced moderately fatty livers similar to those seen in protein-deficient animals.4. Since animals have varying ability to conserve body nitrogen when they are fed on diets limiting in different essential amino acids, measurements of biological value (BV) and net protein utilization by conventional methods, over a short period of time, over-estimate nutritive value relative to amino acid score and probably over-estimate the true nutritive value of poor-quality proteins, particularly those limiting in lysine. If so, this is a serious error, since it leads to underestimates of the protein requirements if BV is used. The fact that certain tissues, particularly the liver, do not necessarily lose nitrogen in proportion to total body nitrogen and may show specific pathological effects depending on the limiting amino acid or the proportions of amino acids in the diet also indicates that general measures of nitrogen economy may not be sufficiently discriminating tests of the nutritive value of proteins.

Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans

1992 ◽  
Vol 263 (5) ◽  
pp. E928-E934 ◽  
Author(s):  
K. S. Nair ◽  
R. G. Schwartz ◽  
S. Welle
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Metabolism

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.

scholarly journals Plasma Amino Acids Metabolomics' Important in Glucose Management in Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Abdelrahim Alqudah ◽  
Mohammed Wedyan ◽  
Esam Qnais ◽  
Hassan Jawarneh ◽  
Lana McClements
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Amino Acids ◽  
Amino Acid ◽  
Fasting Blood Glucose ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Amino Acid Profile ◽  
Healthy Controls

The perturbation in plasma free amino acid metabolome has been observed previously in diabetes mellitus, and is associated with insulin resistance as well as the onset of cardiovascular disease in this population. In this study, we investigated, for the first time, changes in the amino acid profile in a group of people with and without type 2 diabetes (T2D) with normal BMI, from Jordan, who were only managed on metformin. Twenty one amino acids were evaluated in plasma samples from 124 people with T2D and 67 healthy controls, matched for age, gender and BMI, using amino acids analyser. Total amino acids, essential amino acids, non-essential amino acids and semi-essential amino acids were similar in T2D compared to healthy controls. Plasma concentrations of four essential amino acids were increased in the presence of T2D (Leucine, p &lt; 0.01, Lysine, p &lt; 0.001, Phenylalanine, p &lt; 0.01, Tryptophan, p &lt; 0.05). On the other hand, in relation to non-essential amino acids, Alanine and Serine were reduced in T2D (p &lt; 0.01, p &lt; 0.001, respectively), whereas Aspartate and Glutamate were increased in T2D compared to healthy controls (p &lt; 0.001, p &lt; 0.01, respectively). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p &lt; 0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2D compared to healthy controls (p &lt; 0.01). These amino acids were also correlated with fasting blood glucose and HbA1c (p &lt; 0.05). Glutamate, glycine and arginine were correlated with the duration of metformin treatment (p &lt; 0.05). No amino acid was correlated with lipid profiles. Disturbances in the metabolism of these amino acids are closely implicated in the pathogenesis of T2D and associated cardiovascular disease. Therefore, these perturbed amino acids could be explored as therapeutic targets to improve T2D management and prevent associated cardiovascular complications.

scholarly journals Variations with energy nutrition in the concentrations of amino acids of the blood plasma in the dairy cow

1969 ◽  
Vol 23 (3) ◽  
pp. 547-557 ◽  
Author(s):  
A. F. Halfpenny ◽  
J. A. F. Rook ◽  
G. H. Smith
Keyword(s):  
Amino Acids ◽  
Glutamic Acid ◽  
Dairy Cow ◽  
Plasma Concentrations ◽  
Milk Proteins ◽  
Essential Amino Acids ◽  
Lactating Cows ◽  
Regular Change ◽  
Amino Acid Levels ◽  
Friesian Cows

1. The plasma levels of individual amino acids were studied in dairy cows under different conditions of production and energy nutrition.2. A preliminary experiment was conducted which established that there was no regular change in amino acid levels with time of sampling in animals offered food twice daily at milking.3. For animals in the 8th month of pregnancy plasma concentrations of lysine, valine, serine and isoleucine were higher, and of threonine lower, in Jersey than in Friesian cows. Lactation was accompanied in most cows by a fall in the plasma concentrations of lysine, arginine, threonine, histidine, glutamic acid, leucine and alanine and a rise in the level of glycine.4. In lactating cows an improvement in the plane of energy nutrition was associated on average with an increase in the plasma concentrations of ‘non-essential’ amino acids and a decrease in the concentrations of ‘essential’ amino acids.5. Intraruminal infusion of propionic acid in the lactating cow increased the concentrations of certain ‘non-essential’ amino acids, glutamic acid in particular, and decreased those of most other ‘essential’ and ‘non-essential’ amino acids.6. These observations are discussed in terms of the possibility that an increased output of amino acids in milk proteins results in a depression in the concentrations of the ‘essential’ and certain of the ‘non-essential’ animo acids in the plasma. The hypothesis is put forward that the plasma supply of the other ‘non-essential’ amino acids, glutamic acid and proline in particular, may limit synthesis of milk proteins.

Compartmental distribution of amino acids during hemodialysis-induced hypoaminoacidemia

2006 ◽  
Vol 290 (4) ◽  
pp. E643-E652 ◽  
Author(s):  
Elisabet Børsheim ◽  
Hisamine Kobayashi ◽  
Daniel L. Traber ◽  
Robert R. Wolfe
Keyword(s):  
Amino Acids ◽  
Plasma Concentration ◽  
Interstitial Fluid ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Stable Isotope Tracer ◽  
Isotope Tracer ◽  
Intracellular Concentrations ◽  
Muscle Biopsies ◽  
Amino Acid Concentrations

The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relatively constant under a variety of conditions. However, the effect of a decrease in blood amino acid concentrations on intracellular concentrations is not clear. Similarly, the relation between intracellular and interstitial concentrations has not been determined in this circumstance. Thus the aim of this study was to determine the effect of hypoaminoacidemia on intracellular, interstitial, and plasma concentrations of EAA and the mechanisms responsible for the respective changes. Twelve normal pigs were investigated before and during 120 min of hemodialysis by use of stable-isotope tracer methodology, microdialysis technique, and muscle biopsies. During hemodialysis, there was a decrease in the interstitial fluid concentrations of phenylalanine, leucine, alanine, and lysine that corresponded to their decrease in plasma concentration. Nonetheless, the intracellular concentrations of these amino acids were maintained at the basal levels throughout the entire period due principally to a reduction in the rate of incorporation of amino acids into protein that was approximately equivalent to the decrease in uptake from the plasma. In conclusion, intracellular concentrations of amino acids are regulated to maintain relatively constant values, even when plasma and interstitial concentrations fall as a consequence of hemodialysis.

Effects of epinephrine infusion on leucine and alanine kinetics in humans

1984 ◽  
Vol 247 (2) ◽  
pp. E166-E172 ◽  
Author(s):  
J. M. Miles ◽  
S. L. Nissen ◽  
J. E. Gerich ◽  
M. W. Haymond
Keyword(s):  
Amino Acids ◽  
Plasma Concentration ◽  
Carbon Flux ◽  
De Novo ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Essential Amino Acids ◽  
De Novo Synthesis ◽  
Epinephrine Infusion ◽  
Plasma Leucine

Infusion of epinephrine in humans increases glucose production and decreases plasma concentrations of some essential amino acids such as leucine, while not affecting the plasma concentration of the potential gluconeogenic amino acid alanine. To determine whether epinephrine alters alanine and leucine metabolism, rates of appearance (Ra) and disappearance (Rd) of glucose, alanine, and leucine were determined in postabsorptive volunteers using [3H]glucose, [2H3]alanine, [15N]leucine, and [2H3]leucine during a 180-min infusion of epinephrine (50 ng X kg-1 X min-1). Plasma glucose (90 +/- 1 to 142 +/- 5 mg/dl) and insulin (10 +/- 1 to 16 +/- 2 micrograms/ml) increased (P less than 0.05), whereas plasma alanine concentrations did not change and plasma leucine concentrations increased (127 +/- 5 to 72 +/- 3 microM). Glucose Ra increased transiently and returned to basal values by 120 min. In contrast, alanine Ra and Rd increased identically and progressively from 5.7 +/- 0.5 to 14.5 +/- 1.9 mumol X kg-1 X min-1 by 180 min. Although leucine nitrogen Ra increased transiently and returned to basal values, leucine carbon Ra and Rd decreased (P less than 0.05) during the infusion of epinephrine. The calculated rate and percent of leucine nitrogen going to alanine increased, whereas the percent of alanine nitrogen derived from leucine remained constant. The increase in alanine Ra was entirely attributable to increased de novo synthesis because proteolysis, as estimated by leucine carbon flux, decreased.

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