Leucine is a safe, essential amino acid; there is limited evidence that combined branched-chain amino acids (BCAAs) improve appetite, but clinical trials have not supported other claims.
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Description
Leucine is an essential BCAA.
Food Sources
Most protein-containing foods
Mechanism/Pharmacokinetics
- The hydrophobicity of BCAAs (leucine, isoleucine, and valine) make them important to protein formation; BCAAs also affect response to infection (1).
- BCAAs make up about a third of muscle protein and are an important constituent of other tissues (2). Leucine stimulates protein synthesis in muscle.
- The plasma half-life of leucine is 5 days.
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Clinical Trials
- Ergogenics
- Exercise significantly decreases leucine levels. A review of leucine supplementation and intensive exercise noted that leucine supplementation (200 mg/kg) 50 minutes before running had no effect on performance (2).
- A randomized double-blind crossover study in 20 male track and field power athletes compared leucine (50.0 ± 3.3 mg/kg body weight daily) with placebo for 10 weeks and found that leucine supplementation prevented decreased serum leucine concentrations, compared with placebo (3).
- Muscular dystrophy
- A double-blind, placebo-controlled trial of 96 patients with Duchenne muscular dystrophy were randomized to placebo or leucine (0.2 g/kg/day) for a year; no benefit for leucine was demonstrated in terms of muscle strength, joint contracture, functional grade and activity, and pulmonary function tests (4).
- BCAA and phenylketonuria
- A mixture of valine, isoleucine, and leucine was administered to 16 adolescents and young adults with phenylketonuria in a double-blind crossover study comprising four 3-month periods (5). Time to completion of the Attention Diagnostic Methods (which requires substantial attention with mental processing) was significantly faster during the period in which the amino acid mixture was administered. There was not a significant change seen on the Continuous Performance Test.
- BCAA in amyotrophic lateral sclerosis (ALS)
- A double-blind, placebo-controlled trial compared BCAAs (L-leucine 12 g, isoleucine 8 g, and L-valine 6.4 g with pyridoxal phosphate, 160 mg daily) to L-threonine (4 g daily) or placebo for 6 months in 95 patients with ALS (6). Every 2 months, muscle strength, muscle torque, forced vital capacity (FVC), activities of daily living involving upper and lower limbs, and timed tasks were tested. Both the placebo group and the threonine group lost weight, whereas the BCAA-supplemented group gained weight; the difference was significant. Estimated decline in FVC was 2.5 times greater in both groups supplemented with amino acids, compared with placebo. No other significant differences were seen among treatment groups. The amino acids were well tolerated, but the authors point out that adverse effects of these amino acids on pulmonary function could not be ruled out. Long-term effects of this mixture also are unknown.
- Another trial of BCAAs for ALS was halted after 126 participants were recruited because of what appeared to be excess mortality among randomized active treatment (24 BCAAs, 13 placebo); there was also no evidence of efficacy in disability scales between the two groups (7).
- BCAA and tardive dyskinesia (TD)
- An uncontrolled 2-week trial in nine men with neuroleptic-induced TD tested administration of a BCAA medical food three times a day for 2 weeks (8). Compared with baseline, frequency of TD movements (collected by videotape and analyzed in blinded random sequence) decreased significantly; movements decreased at least 38% in all participants.
- BCAA and appetite
- A double-blind study in 28 cancer patients compared BCAA (4.8 g daily) with placebo; improvements in appetite were seen in 55% of the treatment group compared with 16% of those in the placebo group (9).
- BCAA in protein wasting associated with bedrest
- Nineteen healthy participants were randomized into two groups; one group received 30 µmol/day of BCAAs, whereas the other received the same amount of nonessential amino acids. BCAA supplementation attenuated nitrogen loss during short-term bedrest (10).
Other Claimed Benefits/Actions
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Factors Increasing Availability/Absorption
- Maple syrup urine disease (MSUD) or branched chain
-ketoaciduria is the group of inherited disorders of leucine, isoleucine, and valine metabolism. Infants do not manifest symptoms until they start eating protein-containing food; the most deficient in enzymes may die within 10 days of birth. Progressive neurologic dysfunction and urine and ear wax that smell of caramel or maple syrup characterize this disease. Screening should be done in the first week of life. Long-term management of MSUD involves dietary manipulation designed to maintain plasma concentrations of BCAAs 3 to 4 hours after a meal in a specific range (isoleucine, 40 to 90 µmol; leucine, 80 to 200 µmol; and valine, 200 to 425 µmol).
Laboratory Tests
- 78 to 176 µmol/L venous blood
- Urinary output 809 µmol/24 hours
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