- L-alpha-aminoisocaproic acid
- Branched-chain amino acid (BCAA)
For Patients & Caregivers
How It Works
Leucine is an essential amino acid required for muscle growth and maintenance.
Leucine is an amino acid that is not made in the human body and is required for muscle maintenance. Therefore, it has to be obtained through dietary sources rich in protein such as dairy, soy, and meats. Leucine is also available as a dietary supplement and is used to improve muscle strength and endurance.
Studies evaluating leucine suggest it may be useful in some populations to prevent or treat loss of skeletal muscle mass and strength, known as sarcopenia. Leucine can also increase insulin secretion, but did not improve sugar levels in diabetic patients.
- Muscle strength and endurance
Some studies show that leucine improves muscle strength and endurance, although it is unclear whether these effects are due to leucine, and not to exercise itself.
In one study, leucine did not affect blood sugar levels in diabetic men. Further research is needed.
Leucine may be useful in some populations to prevent or treat loss of skeletal muscle mass and strength. More studies are needed as results are mixed across various populations including frail, elderly, obese, and critically ill patients.
Do Not Take If
- You are taking insulin and other antidiabetic medications: Leucine can stimulate insulin secretion and may further lower blood glucose levels.
- You have maple syrup urine disease: Leucine can accumulate in blood or urine resulting in dysfunction of nerve cells.
- You are taking phosphodiesterase 5 (PDE5) inhibitors (sildenafil): In animal studies, leucine increased the effects of these drugs .
For Healthcare Professionals
Leucine is an essential amino acid that is not synthesized in the human body and must be obtained from food consisting of plant or animal protein. Leucine is often used together with valine and isoleucine, which are branched-chain amino acids (BCAA), in parenteral forms for nutritional support to maintain nitrogen balance, and to treat cirrhosis and hepatic encephalopathy.
Purified leucine is marketed as a dietary supplement for body building. It is thought to stimulate protein synthesis by activating the mammalian target of rapamycin (mTOR) pathway (1) (2). In various animal models, leucine supplementation improved leptin sensitivity (18) (19), lipid and glucose metabolism (19), exercise tolerance (20) , acquired growth hormone resistance (21), disease-related skeletal muscle dysfunctions (22), and anemia (23).
An oral leucine-enriched BCAA mixture increased muscle protein synthesis and reversed sarcopenic processes in cirrhotic patients (24). However, leucine supplementation alone did not have additional effects on exercise capacity, muscle mass or quality of life when compared with exercise plus leucine supplementation (25). Leucine did not affect glycemic control in elderly diabetic men (5), but in healthy subjects and in the presence of glucose, stimulated insulin secretion and lowered blood glucose levels (8).
Studies with leucine supplementation and exercise show some benefits in older populations. A leucine-rich essential amino acid mixture along with exercise significantly improved muscle mass and strength, and walking speed in community-dwelling sarcopenic women (26). Leucine-enriched whey protein nutritional supplements improved sarcopenia in older and older-obese adults (27) (28). Another study evaluating combined resistance training with high-dose leucine supplementation in older adults suggests moderate benefit on muscle strength and functional status (29).
In athletes, dietary supplementation with leucine can improve performance (3) and upper body strength (4). However, two double-blind RCTs in younger active populations, one of resistance training along with powdered leucine/protein shakes in young men (30), and another evaluating a postsurgical rehabilitation program along with leucine supplementation among athletes (31) did not find improvements attributable to leucine, although it appeared to promote thigh muscle recovery in the latter study (31).
Findings from systematic reviews are mixed. In older sarcopenia-prone individuals leucine supplementation may improve body weight, body mass index, and lean body mass, but not muscle strength (32). Another review concluded that although central leucine injection decreased food intake, this effect was not well reproduced with oral leucine, even though it improved glucose homeostasis (33). Well designed longer-term studies are needed to determine optimal supplementation with leucine across these varied populations.
Leucine from dietary sources is generally considered safe. However, excessive intake may result in hypoglycemia (8) and may also cause vitamin B3 and B6 deficiencies (9) (10). Amounts exceeding ∼39 g/d may pose a health risk (17). Animal pancreatic cancer models suggest that it may also increase growth of pancreatic tumors (34).
Mechanism of Action
Leucine is among the essential branched-chain amino acids (BCAA) associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors (35). It stimulates protein synthesis by activating the mammalian target of rapamycin (mTOR) pathway (1) and is thought to enhance muscle anabolic signaling (11).
Animal models indicate that BCAA metabolism-related gene expression is regulated during adipocyte differentiation and influenced by nutrient levels, and leucine supplementation induced Bcat2 and Bckdha genes during early and late differentiation (35). It improved insulin sensitivity in high-fat diet-fed mice by decreasing adiposity, rather than through direct action on peripheral target organs (36). Leucine supplementation also improved lipid and glucose metabolism and restored leptin sensitivity in previously obese animals (19). At the same time, in already-obese rats, leucine supplementation worsened adiposity by encouraging hypothalamic gene expression that favored fat accumulation (37). In another animal study, it did not reduce food intake or induce an anorectic pattern of hypothalamic gene expression (38). Co-ingested leucine and glycine markedly attenuated glucose response, with only a modest increase in insulin response, suggesting their effects on glucose metabolism are partially insulin-independent (39). Leucine along with subtherapeutic levels of a PDE5 inhibitor altered lipid metabolism from storage to oxidation, improved glycemic control, and reversed hepatic steatosis induced by high-fat feeding (40).
Leucine supplementation speeds connective tissue repair and muscle regeneration by attenuating transforming growth factor-beta type I receptor and activating Smad2/3 (41). Antiatrophic effects were not mediated by its metabolite, beta-hydroxy-beta-methyl butyrate, and did not occur in dexamethasone-treated rats (42).
The ability of leucine to improve anemia in ribosomal protein-deficient cells occurs independently of TP53 (23). In Diamond-Blackfan anemia patients, leucine modulates protein synthesis by enhancing translation leading to improved hemoglobin levels (7). In the skeletal muscle of cirrhotic patients, an oral leucine-enriched BCAA mixture increased autophagy and reversed impaired mTOR1 signaling (24).
- Insulin and other antidiabetic medications: Leucine can stimulate insulin secretion and may have additive hypoglycemic effects (8) (43).
- Vitamin B3 and vitamin B6: Leucine can interfere with synthesis of these vitamins (9) (10).
- Phosphodiesterase 5 (PDE5) inhibitors (sildenafil): Animal models indicate leucine may have synergistic effects (40).