Thirteen-Week Oral Toxicity Study of Branched-Chain Amino Acids in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Toyohisa Katsumata ◽  
Nobuo Nishimura ◽  
Kazunori Mawatari ◽  
...  
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Ketone Bodies ◽  
Body Weight Gain ◽  
Recovery Period ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Standard Diet ◽  
Oral Toxicity ◽  
Branched Chain

Branched-chain amino acids (l-isoleucine, l-valine, and l-leucine) are being increasingly used in sport supplements. This study evaluated toxicological and behavioral effects of l-isoleucine (Ile), l-valine (Val), and l-leucine (Leu) during a dosing study with male and female Sprague-Dawley rats. The amino acids were incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w). A control group of rats received a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine stability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. No significant, dose-related effects on body weight were found in rats fed a Leu-and Ile-supplemented diet. Val mixed into a diet at 5.0% ( w/ w) decreased slightly, but significantly body weight gain in females, but not males. Ile (5.0% w/ w) affected the urine electrolytes, protein, ketone bodies, urine glucose, and urobilinogen in both genders, yet the observed changes remained mostly within the range observed in controls. The random findings in hepatology and ophthalmology at the 13-week sacrifice were not considered toxicologically relevant to effects of the tested amino acids. No significant changes in organ weights were recorded. We estimate the no-observed-adverse-effect level (NOAEL) for Ile at 2.5% for both genders (male, 1.565 ± 0.060 g/kg/day; females, 1.646 ± 0.095 g/kg/day), Val at 5.0% for males (3.225 ± 0.135 g/kg/day) and 2.5% for females (1.853 ± 0.060 g/kg/day), and Leu at 5.0% for both genders (males, 3.333 ± 0.101 g/kg/day: females, 3.835 ± 0.257 g/kg/day).

Thirteen-Week Oral Toxicity Study of l-Glutamine in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Kazunori Mawatari ◽  
Miro Smriga ◽  
Takeshi Kimura
Keyword(s):  
Ketone Bodies ◽  
Recovery Period ◽  
Control Group ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Urine Ph ◽  
Toxicological Effects ◽  
Adverse Effect Level ◽  
Hematology Parameters

l-Glutamine (Gln) is a semiessential amino acid used in enteral feeding in critically ill patients, and is contained in numerous dietary supplements available to the general public. This study evaluated toxicological effects of Gln in male and female Sprague-Dawley rats. Gln produced by Ajinomoto Co. (Tokyo, Japan) was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w), respectivelly. A control group of rats received only a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. Throughout the administration and recovery periods, no deaths were observed, and no changes in diet consumption, ophthalmologic findings, gross pathology, and histopathology were detected. Several changes in urine parameters (total protein, urine pH, and a positive incidence (±) of ketone bodies) were observed in the 2.5% and 5.0% groups at the end of the administration period. Minor increases were found in hematology parameters for the 5.0% group (platelet count, γ-globulin, lactate dehydrogenase [LDH]), but all changes were within physiological range. No effects of administration were observed in the 1.25% group. The no-observed-adverse-effect level (NOAEL) for Gln was estimated at 1.25% for both genders (males 0.83 ± 0.01 g/kg/day; females, 0.96 ± 0.06 g/kg/day).

scholarly journals Impaired Skeletal Muscle Branched-Chain Amino Acids Catabolism Contributes to Their Increased Circulating Levels in a Non-Obese Insulin-Resistant Fructose-Fed Rat Model

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 355 ◽  
Author(s):  
Jérémie David ◽  
Dominique Dardevet ◽  
Laurent Mosoni ◽  
Isabelle Savary-Auzeloux ◽  
Sergio Polakof
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Body Weight ◽  
Branched Chain Amino Acids ◽  
Laboratory Animals ◽  
Standard Diet ◽  
Elevated Blood ◽  
High Fat ◽  
Insulin Resistant ◽  
Branched Chain

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat–fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat–fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism.

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

scholarly journals Effect of abomasal glucose infusion on alanine metabolism and urea production in sheep

2000 ◽  
Vol 84 (2) ◽  
pp. 157-163 ◽  
Author(s):  
T. Obitsu ◽  
D. Bremner ◽  
E. Milne ◽  
G. E. Lobley
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Branched Chain Amino Acids ◽  
Flux Rate ◽  
Plasma Urea ◽  
Exogenous Glucose ◽  
Abomasal Infusion ◽  
Urea Production ◽  
Branched Chain ◽  
N Flux

The effect of abomasal infusion of glucose (120 kJ/d per kg body weight (BW)0·75, 758 mmol/d) on urea production, plasma alanine-N flux rate and the conversion of alanine-N to urea was studied in sheep offered a low-N diet at limited energy intake (500 kJ/d per kg BW0·75), based on hay and grass pellets. Glucose provision reduced urinary N (P= 0·040) and urea (P= 0·009) elimination but this was offset by poorer N digestibility. Urea-N production was significantly reduced (822v. 619 mmol/d,P= 0·024) by glucose while plasma alanine-N flux rate was elevated (295v. 342 mmol/d,P= 0·011). The quantity of urea-N derived from alanine tended to be decreased by glucose (127v. 95 mmol/d) but the fraction of urea production from alanine was unaltered (15 %). Plasma urea and alanine concentrations (plus those of the branched chain amino acids) decreased in response to exogenous glucose, an effect probably related to enhanced anabolic usage of amino acids and lowered urea production.

BCAA intake affects protein metabolism in muscle after but not during exercise in humans

2001 ◽  
Vol 281 (2) ◽  
pp. E365-E374 ◽  
Author(s):  
Eva Blomstrand ◽  
Bengt Saltin
Keyword(s):  
Amino Acids ◽  
Recovery Period ◽  
Aromatic Amino Acids ◽  
Branched Chain Amino Acids ◽  
Cycle Exercise ◽  
Placebo Condition ◽  
Muscle Concentration ◽  
Branched Chain ◽  
Sparing Effect ◽  
Exercise In Humans

Branched-chain amino acids (BCAA) or a placebo was given to seven subjects during 1 h of ergometer cycle exercise and a 2-h recovery period. Intake of BCAA did not influence the rate of exchange of the aromatic amino acids, tyrosine and phenylalanine, in the legs during exercise or the increase in their concentration in muscle. The increase was ∼30% in both conditions. On the other hand, in the recovery period after exercise, a faster decrease in the muscle concentration of aromatic amino acids was found in the BCAA experiment (46% compared with 25% in the placebo condition). There was also a tendency to a smaller release (an average of 32%) of these amino acids from the legs during the 2-h recovery. The results suggest that BCAA have a protein-sparing effect during the recovery after exercise, either that protein synthesis has been stimulated and/or protein degradation has decreased, but the data during exercise are too variable to make any conclusions about the effects during exercise. The effect in the recovery period does not seem to be mediated by insulin.

scholarly journals Metabolic consequences of methylenecyclopropylglycine poisoning in rats

1991 ◽  
Vol 274 (2) ◽  
pp. 395-400 ◽  
Author(s):  
K Melde ◽  
S Jackson ◽  
K Bartlett ◽  
H S A Sherratt ◽  
S Ghisla
Keyword(s):  
Amino Acids ◽  
Ketone Bodies ◽  
Blood Glucose Concentration ◽  
Plasma Concentrations ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Oxidation Products ◽  
Rat Liver Mitochondria ◽  
Toxic Metabolite ◽  
Branched Chain

We describe the effects of methylenecyclopropylglycine in fasted rats. A 75% decrease in the blood glucose concentration and an increase of lactate and pyruvate were observed 6 h after administration of 100 mg of this amino acid/kg. By contrast with the effects reported for hypoglycin [Williamson & Wilson (1965) Biochem. J. 94, 19c-21c], the plasma concentrations of ketone bodies decreased after administration of methylenecyclopropylglycine and the concentrations of branched-chain amino acids in the plasma were increased 6-fold. The oxidation of decanoylcarnitine or of palmitate was nearly completely inhibited in rat liver mitochondria from methylenecyclopropylglycine-poisoned rats. The activities of acetoacetyl-CoA and of 3-oxoacyl-CoA thiolase were decreased to 25% and less than 10% of the controls. There was a pronounced aciduria, due to the excretion of dicarboxylic acids and of oxidation products of branched-chain amino acids. The accumulation of the toxic metabolite methylenecyclopropylformyl-CoA in the mitochondrial matrix was detected after administration of methylenecyclopropylglycine. Similarly we confirmed experimentally that methylenecyclopropylacetyl-CoA accumulates in mitochondria incubated with methylenecyclopropylpyruvate.

Tumour and Host Tissue Responses to Branched-Chain Amino Acid Supplementation of Patients with Cancer

1994 ◽  
Vol 86 (3) ◽  
pp. 339-345 ◽  
Author(s):  
M. A. McNurlan ◽  
S. D. Heys ◽  
K. G. M. Park ◽  
J. Broom ◽  
D. S. Brown ◽  
...  
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Cancer Patients ◽  
Muscle Tissue ◽  
Branched Chain Amino Acids ◽  
Saline Control ◽  
Intravenous Nutrition ◽  
Branched Chain

1 Rates of protein synthesis have been measured from the incorporation of 57 mg of l-[1-13C]leucine/kg for 90 min into muscle tissue and colorectal tumours removed at surgery from cancer patients. 2. For the 20 h preceding surgery and during the measurement of protein synthesis, the patients received intravenous saline, conventional intravenous nutrition (0.2 g of N and 103 non-protein kJ/kg body weight) or intravenous nutrition enriched with the branched-chain amino acids leucine, isoleucine and valine (0.2 g of N with 30% from branched-chain amino acids and 103 non-protein kJ/kg body weight). 3. Conventional intravenous nutrition resulted in a significant stimulation of the rate of protein synthesis in both muscle tissue (2.64 ± 0.75%/day versus 1.78 ± 0.51%/day in saline control, means ± SD) and tumour tissue (43.9 ± 10.3%/day versus 22.6 ± 5.6%/day in saline control). 4. Pre-operative nutrition enriched with branched-chain amino acids was less effective than conventional intravenous nutrition in stimulating protein synthesis in both muscle and tumour. The rates of protein synthesis were 2.12 ± 0.41%/day in muscle and 33.7 ± 5.3%/day in the tumours. 5. The expression of proliferating cell nuclear antigen in sections of the tumours showed changes with intravenous feeding of the two different amino acid mixtures that were similar to the changes in protein synthesis, and these two variables were significantly correlated. This is evidence that feeding with conventional mixtures and mixtures enriched with branched-chain amino acids stimulates tumour growth. 6. In this study the mixture enriched with branched-chain amino acids provided no clear advantage for cancer patients, since a smaller response to branched-chain amino acids was observed in both tumours and host muscle tissue.

scholarly journals Growth rate and acid-base balance in turkeys fed a silage-containing diet modified by different dietary cation-anion difference

2017 ◽  
Vol 73 (12) ◽  
pp. 786-791
Author(s):  
Kamil Gruszczyński ◽  
Wacław Strobel ◽  
Marta Wójcik ◽  
Urszula Kosior-Korzecka ◽  
Joanna Wessely-Szponder ◽  
...  
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Diet Group ◽  
Control Group ◽  
Standard Diet ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance ◽  
Group B ◽  
Group D

The aim of the study was to find the responses of acid-base parameters and performance parameters of turkeys to a corn silage (CS) diet with different values of the dietary cation-anion difference (DCAD). The turkeys were fed as follows: group A (control) – standard diet (SD) (60%) plus CS (40%); group B – SD (60%), CS (40%) plus 240 g of CaCl2 per100 kg of diet; group C – SD (60%), CS (40%) plus 480 g of CaCl2 per 100 kg of diet; group D – SD (60%), CS (40%) plus 240 g of NaHCO3 per 100 kg of diet; group E – SD (60%), CS (40%) plus 480 g NaHCO3 per 100 kg of diet. The addition of the smaller amount of CaCl2 reduced DCAD, which ranged between 49.75 ± 6.29 mEq/kg DM and 93.56 ± 3.34 mEq/kg DM. An increased content of CaCl2 led to high, negative values of DCAD. NaHCO3 supplemented in both doses resulted in a significant elevation of DCAD. The addition of CS to the SD led to a lower body weight in comparison to that in the B, C, D and E groups. Forage acidification and alkalization improves body weight gain (BWG) at every stage of feeding. Compared to the control group, the anion gap was insignificantly lower in birds exposed to the acidic diet, and was comparable to the decrease in HCO3 –. Conversely, the addition of NaHCO3 to the diet led to a marked elevation in HCO3 – to 29.63 ± 0.4 mEq/L in group D and to 30.3 ± 0.69 mEq/l in group E. In conclusion, a change in DCAD during the feeding of forage containing CS exerts stimulatory effects on productive parameters of turkeys....

scholarly journals Branched-Chain Amino Acids Have Equivalent Effects to Other Essential Amino Acids on Lifespan and Aging-Related Traits in Drosophila

2019 ◽  
Vol 75 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Paula Juricic ◽  
Sebastian Grönke ◽  
Linda Partridge
Keyword(s):  
Amino Acids ◽  
Control Diet ◽  
Essential Amino Acids ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Dependent Manner ◽  
Dietary Nitrogen ◽  
Compensatory Feeding ◽  
Age Related ◽  
Branched Chain

Abstract Branched-chain amino acids (BCAAs) have been suggested to be particularly potent activators of Target of Rapamycin (TOR) signaling. Moreover, increased circulating BCAAs are associated with higher risk of insulin resistance and diabetes in both mice and humans, and with increased mortality in mice. However, it remains unknown if BCAAs play a more prominent role in longevity than do other essential amino acids (EAAs). To test for a more prominent role of BCAAs in lifespan and related traits in Drosophila, we restricted either BCAAs or a control group of three other EAAs, threonine, histidine and lysine (THK). BCAA restriction induced compensatory feeding, lipid accumulation, stress resistance and amelioration of age-related gut pathology. It also extended lifespan in a dietary-nitrogen-dependent manner. Importantly, the control restriction of THK had similar effects on these phenotypes. Our control diet was designed to have every EAA equally limiting for growth and reproduction, and our findings therefore suggest that the level of the most limiting EAAs in the diet, rather than the specific EAAs that are limiting, determines the response of these phenotypes to EAA restriction.

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