Leucine

Branched-chain amino acids/Drug Interactions:

  • AnalgesicsAnalgesics: In humans, administration of neuroleptic anesthesia and general anesthesia with halothane resulted in significant increases in branched-chain amino acids (BCAAs) (70), which may result in a further decrease in response to pain (71).
  • AnestheticsAnesthetics: In humans, administration of neuroleptic anesthesia and general anesthesia with halothane resulted in significant increases in BCAAs (70).
  • AntidiabeticsAntidiabetics: In human research, insulin administration decreased the plasma/intracellular concentration of BCAAs (73) and all gluconeogenic amino acids, except alanine (72). In humans, insulin resulted in a dose-dependent suppression of endogenous leucine (73). In humans, concomitant administration of glucose and amino acids decreased the concentration of amino acids (68), stimulated insulin secretion, and lowered blood glucose (32). Compared to placebo, participants administered CHO and BCAAs showed increased plasma glucose levels (p<0.05) (33). In cross-country runners administered BCAAs, significantly decreased levels of glucose after exercise compared to before the race were noted (5.2 ? 0.7 vs. 5.9 ? 0.6mmol/L, respectively; p<0.01) (3).
  • AntineoplasticsAntineoplastics: In vitro, BCAAs reduced the growth and mRNA expression of some liver cancer (hepatocellular carcinoma) cells through protein synthesis inhibition (25; 74).
  • Athletic performance enhancersAthletic performance enhancers: In humans, BCAA administration during sustained intense exercise may prevent or decrease the rate of protein degradation caused by heavy exercise by preventing increases in plasma and muscle tyrosine and phenylalanine concentrations, possibly through prevention of metabolism by skeletal muscle (4).
  • CaffeineCaffeine: In humans, oral administration of caffeine lowered plasma BCAA levels following fatigue-inducing mental tasks (75).
  • CorticosteroidsCorticosteroids: In humans, acute depletion of glutamine increased leucine oxidation in patients being treated with prednisone (76).
  • DiazoxideDiazoxide: According to secondary sources, diazoxide may decrease the effects of BCAAs on proteins.
  • EpinephrineEpinephrine: In humans, plasma/intracellular concentrations of BCAAs and all gluconeogenic amino acids, except alanine, decreased after epinephrine administration (72).
  • Human growth hormone (HGH)Human growth hormone (HGH): In humans, BCAAs were increased during high levels of human growth hormone (77).
  • ImmunosuppressantsImmunosuppressants: In vitro research showed that phytohemagglutinin (PHA)-stimulated lymphocytes require alanine and serine in addition to 13 other amino acids present in Eagle's minimal essential medium (arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine) and that omission of any of these amino acids would stop almost completely the proliferation of PHA-stimulated lymphocytes (78).
  • Insulin preparationsInsulin preparations: In humans, plasma/intracellular concentrations of BCAAs and all gluconeogenic amino acids, except alanine, decreased after insulin administration (72). In humans, insulin resulted in a dose-dependent suppression of endogenous leucine (73).
  • Recombinant human erythropoietin (rhEPO)Recombinant human erythropoietin (rhEPO): In humans, correction of anemia with recombinant human erythropoietin (rhEPO) caused levels of BCAAs to also return to normal levels (79). In animal research, renal anemia is associated with decreased levels of BCAAs, and these levels could be recovered following rhEPO treatment (80).
  • Thyroid hormonesThyroid hormones: According to secondary sources, thyroid hormone medications may decrease the rate of BCAA metabolism. After crossing over to the BCAA group, participants in a clinical trial showed increased T3 levels and increased ratio of T3 to T4 (p<0.05) (34).

    • Branched-chain amino acids/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: In humans, administration of neuroleptic anesthesia and general anesthesia with halothane resulted in significant increases in BCAAs (70), which may result in a further decrease in response to pain (71).
  • AntineoplasticsAntineoplastics: In vitro, BCAAs reduced the growth and mRNA expression of some liver cancer (hepatocellular carcinoma) cells through protein synthesis inhibition (25; 74).
  • Athletic performance enhancersAthletic performance enhancers: In humans, BCAA administration during sustained intense exercise may prevent or decrease the rate of protein degradation caused by heavy exercise by preventing increases in plasma and muscle tyrosine and phenylalanine concentrations, possibly through prevention of metabolism by skeletal muscle (4).
  • CaffeineCaffeine: In humans, oral administration of caffeine lowered plasma BCAA levels following fatigue-inducing mental tasks (75).
  • CreatineCreatine: In humans, creatine in combination with 7g of leucine failed to stimulate insulin release (81).
  • GlutamineGlutamine: A combination of glutamine and leucine increased insulin secretion in vitro (82).
  • HypoglycemicsHypoglycemics: In humans, insulin administration may decrease the plasma/intracellular concentration of BCAAs (73) and all gluconeogenic amino acids, except alanine (72). In humans, insulin resulted in a dose-dependent suppression of endogenous leucine (73). In humans, concomitant administration of glucose and amino acids decreased the concentration of amino acids (68), stimulated insulin secretion, and lowered blood glucose (32). Compared to placebo, participants administered CHO and BCAAs showed increased plasma glucose levels (p<0.05) (33). In cross-country runners administered BCAAs, significantly decreased levels of glucose after exercise compared to before the race were noted (5.2 ? 0.7 vs. 5.9 ? 0.6mmol/L, respectively; p<0.01) (3).
  • ImmunomodulatorsImmunomodulators: In vitro research showed that phytohemagglutinin (PHA)-stimulated lymphocytes require alanine and serine in addition to 13 other amino acids present in Eagle's minimal essential medium (arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine) and that omission of any of these amino acids would stop almost completely the proliferation of PHA-stimulated lymphocytes (78).
  • Thyroid agentsThyroid agents: According to secondary sources, thyroid hormone medications may decrease the rate of BCAA metabolism. After crossing over to the BCAA group, participants in a clinical trial showed increased T3 levels and increased ratio of T3 to T4 (p<0.05) (34).

    • Branched-chain amino acids/Food Interactions:

  • CarbohydratesCarbohydrates: In humans, consumption of carbohydrates increased the rate of oxidation of leucine (a branched-chain amino acid) (83). In humans, coingestion of protein and/or leucine with carbohydrates augmented insulin secretion during postexercise recovery (84).
  • Glucose-rich foodsGlucose-rich foods: In humans, concomitant administration of glucose and amino acids decreased the concentration of amino acids (68), stimulated insulin secretion, and lowered blood glucose (32).
  • Ketogenic dietKetogenic diet: In humans, BCAAs as an adjunct to a ketogenic diet in individuals with epilepsy induced a 100% seizure reduction in three out of 17 children and a 50% reduction in five out of 17 patients (85).
  • Protein-rich dietProtein-rich diet: In humans, whey protein increased plasma concentration of BCAAs (2). In humans, coingestion of protein and/or leucine with carbohydrates augmented insulin secretion during postexercise recovery (84).
  • Whey proteinWhey protein: In humans, whey protein increased plasma concentration of BCAAs (2). According to secondary sources, muscle growth is supported by whey protein, a rich source of BCAAs.

    • Branched-chain amino acids/Lab Interactions:

  • Acetyl-carnitineAcetyl-carnitine: Compared to the control group, participants administered BCAAs showed significantly lower plasma levels of acetyl-carnitine at the end of the study (3.4 ? 1.0 to 18.0 ? 1.3mcmol/L vs. 1.8 ? 0.6 to 11.5 ? 1.1mcmol/L, respectively, p<0.05) (9).
  • AlbuminAlbumin: In humans administered BCAAs, reduced albumin levels (73.1 ? 2.8 vs. 63.4 ? 4.5; p<0.01) were noted compared to baseline (35). In subjects taking BCAAs, a significantly greater albumin level maintenance rate was noted compared to control (46% vs. 8% for Alb>0.2; 38% vs. 25% for 0.1>Alb>-0.1; and 15% vs. 67% for Alb<0.2) (61). Overall, this between-group difference was statistically significant (p=0.02). After two years, class two subjects taking BCAAs demonstrated an albumin maintenance rate that was significantly greater than control (44% vs. 0% for Alb>0.2; 44% vs. 33% for 0.1>Alb>-0.1; 11% vs. 67% for Alb<-0.2). Overall, this between-group difference was statistically significant (p=0.02). Also the serum albumin level was significantly higher in the BCAA group in those with Child grade B or C disease or major hepatic resection after six months of treatment compared to the control group (p<0.05) (58).
  • Amino acid concentrationsAmino acid concentrations: In humans, supplementation with BCAAs resulted in a faster decrease in muscle concentrations of aromatic amino acids (7).
  • AmmoniaAmmonia: Compared to the placebo group, participants administered BCAAs showed a statistically significant increase in plasma ammonia levels at point of exhaustion (95 ? 18mcmol/L vs. 135 ? 7mcmol/L, respectively; p<0.001) (43).
  • BilirubinBilirubin: In humans, BCAAs decreased total bilirubin levels (34).
  • Creatine kinaseCreatine kinase: In humans, BCAA administration decreased plasma creatine kinase (47; 48).
  • Free fatty acids (FFAs)Free fatty acids (FFAs): In humans, a carbohydrate plus BCAA solution resulted in lower FFAs (33). Compared to placebo, participants administered CHO or CHO + BCAAs showed significantly increased levels of plasma free fatty acids at 15, 30, 45, 60, and 75 minutes of exercise, as well as at fatigue (+0.5mmol/L and +0.4mmol/L for CHO and CHO + BCAA groups, respectively; p<0.05) (33). In humans administered BCAAs, reduced plasma levels of free fatty acids were observed throughout the exercise period compared to placebo (p=0.01) were noted (43).
  • GlucoseGlucose: In humans, concomitant administration of glucose and amino acids lowered blood glucose (32). Compared to the placebo group, participants administered CHO or CHO + BCAA showed statistically increased plasma glucose (p<0.05) (33). In cross-country runners administered BCAAs, significantly decreased levels of glucose were noted after exercise compared to before the race (5.2 ? 0.7 vs. 5.9 ? 0.6mmol/L, respectively; p<0.01) (3).
  • Granulocyte elastaseGranulocyte elastase: In humans, BCAA administration decreased plasma granulocyte elastase levels (47).
  • Heart rateHeart rate: Participants administered CHO and CHO + BCAA showed a statistically significant reduction in heart rate at fatigue compared to the placebo group (p<0.05) (33).
  • InsulinInsulin: In humans, the mean resting concentration of plasma insulin for the participants receiving a BCAA supplement decreased by 26% (p<0.05) (45). However, in other studies, a carbohydrate-plus-BCAA solution resulted in higher plasma insulin (33; 32).
  • Lactate dehydrogenaseLactate dehydrogenase: In humans, BCAA administration decreased plasma lactate dehydrogenase (47; 48).
  • MethionineMethionine: In humans administered BCAAs, statistically significant reduced levels of methionine (54 ? 31 vs. 52 ? 28mcmol/L, respectively) were shown compared to casein use (34).
  • Nitrogen balanceNitrogen balance: In humans administered BCAAs, a statistically significant 10% reduction in urinary nitrogen levels (7.10 ? 2.33 vs. 6.35 ? 1.81g, respectively) was shown compared to casein use. For the participants who improved and continued treatment for an additional three months, this increase in nitrogen balance was maintained for subjects receiving BCAAs (2.83 ? 1.97g, p<0.001) or casein (2.51 ? 1.78, p<0.05).
  • PhenylalaninePhenylalanine: In humans, BCAAs were shown to enhance mental functioning in patients with phenylketonuria, an inability to breakdown the amino acid, phenylalanine; this result was attributed to BCAAs' potential to compete with phenylalanine (86).
  • PlateletsPlatelets: Compared to the control group, patients with disease of Child grade A who were administered BCAAs showed elevated platelets after six (p<0.05) and nine months (p<0.01).
  • Renal functionRenal function: In humans, a slight but insignificant increase in glomerular filtration rate (GFR) and renal plasma flow (RPF) was observed following BCAA infusion (87), possibly affecting the blood flow through the kidneys, resulting in altered kidney function.
  • Red cell countRed cell count: Compared to the control group, stratified analysis found that subjects with Child grade B and C disease who were administered BCAAs showed statistically significant increase in red cell count after six (p<0.01) and nine months (p<0.05) (58).
  • Respiratory exchange ratio (RER)Respiratory exchange ratio (RER): In humans, RER during the exercise test was significantly lower in the BCAA group than in the placebo group (p<0.05) (41).
  • SodiumSodium: In humans administered BCAAs, sodium (94.8 ? 1.0 vs. 91.4 ? 1.5; p<0.05) levels were significantly reduced compared to baseline (35).
  • ThyroidThyroid: After crossing over to the BCAA group, participants in a clinical trial showed significantly increased T3 levels (58 ? 25 to 75 ? 21ng/dL, p<0.05) and a significantly increased ratio of T3 to T4 (8.3 ? 3.3 to 12.5 ? 5.0, p<0.05) (34).
  • TryptophanTryptophan: In humans administered either low- or high-dose BCAAs, a 12-15% reduction in inward transport of total tryptophan across the blood-brain barrier was noted, while participants administered tryptophan showed a statistically nonsignificant 6.5-fold increase (18). Other studies with administered BCAAs also showed significantly reduced levels of free tryptophan (p<0.05) (43; 3; 34).
  • Urea concentrationUrea concentration: In humans administered BCAAs, a 20% increase in urea concentration was noted after treatment compared to baseline (p<0.02) (35).
  • WeightWeight: Compared to the placebo, participants administered BCAAs showed a statistically significant increase in weight (-1.1 ? 4.7 vs. +0.2 ? 3.3kg, respectively; p=0.04) (38).