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

Abstract

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).

Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet

“…After 15 weeks on HFD, the obese animals were divided into four subgroups of treatment for 6 weeks: i) reference (REF) group (REF, n = 7) receiving the CD; ii) LS group (LS, n = 8) receiving diet supplemented with 5% L-leucine (Ajinomoto Interamericana Indústria e Comércio Ltda, São Paulo, Brazil); iii) endurance training group (ET, n = 8) receiving the CD, and iv) LS plus ET group receiving diet supplemented with 5% L-leucine (LS+ET, n = 7). Other studies used this leucine dose and no toxic effect was reported [22,23]. …”

Determination of the Tolerable upper Intake Level of leucine in Acute men

“…Tsubuku et al (24) in a controlled experiment studied oral supplements of leucine excess in 4-wk-old rats and estimated ;3500 mg Á kg 21 Á d 21 as the no observed adverse effect level based on body weight, food consumption, and hematological measurements. Similarly, Mawatari et al (25) in 10-wk-old female rats estimated that oral leucine at 1000 mg Á kg 21 Á d 21 did not affect the outcome of pregnancy and did not cause fetal toxicity.…”

Bismuth(iii) complexes derived from α-amino acids: the impact of hydrolysis and oxido-cluster formation on their activity against Helicobacter pylori

“…[57][58][59][60][61][62][63][64] In general, the α-amino acids showed no mutagenic activity, no toxicological relevant effects, and no observed deaths. [57][58][59][60][61][62][63][64] In general, the α-amino acids showed no mutagenic activity, no toxicological relevant effects, and no observed deaths.…”