- L-alpha-aminoisocaproic acid
- Branched-chain amino acid (BCAA)
For Patients & Caregivers
Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.
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, fish, soy, meat, poultry, beans, and eggs. 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. However, evidence is inconsistent and because studies often combine leucine with other nutrients, it is hard to know which components may be responsible for potential benefits.
Muscle strength and endurance
Some studies show that leucine improves muscle strength and endurance, but evidence is inconsistent and various products studied also contain additional nutrients.
Leucine may increase insulin secretion, but did not improve blood sugar levels in a clinical study of diabetic men. Further research is needed.
Leucine may be useful in some populations to prevent or treat loss of skeletal muscle mass and strength, but evidence is inconsistent and various products studied also contain additional nutrients. More studies are needed across frail, elderly, obese, and critically ill patient populations.
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 PDE5 inhibitors (sildenafil): Leucine increased the effects of these drugs in animal studies, but clinical significance is not known.
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. It is often used together with valine and isoleucine (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 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).
Although studies of leucine-containing products suggest potential benefit for improving muscle mass and strength across various populations, results are mixed (5) (24) (25) (26) (27) (28) (50) (51), and a systematic review cites high heterogeneity across trial designs and formulas used (32). Other studies have shown that leucine does not affect glycemic control in elderly diabetic men (5), although in healthy subjects and in the presence of glucose, it stimulates insulin secretion and lowered blood glucose levels (8).
Preliminary data suggest that essential amino acids with high levels of leucine may help prevent muscle loss in patients with non small-cell lung cancer (48). The addition of a leucine-rich supplement to a multimodal therapy also improved handgrip strength, but not other measures of physical functioning in advanced cancer patients (52).
Mechanism of Action
Leucine is an essential branched-chain amino acid (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 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 induces Bcat2 and Bckdha genes during early and late differentiation (35). Insulin sensitivity was improved in mice fed a high-fat diet by decreasing adiposity, rather than through direct action on peripheral target organs (36). Supplementation also improved lipid and glucose metabolism and restored leptin sensitivity in previously obese animals (19). However, in already-obese rats, leucine worsened adiposity by encouraging hypothalamic gene expression that favored fat accumulation (37). In another study, it did not reduce food intake or induce an anorectic pattern of hypothalamic gene expression (38). Co-ingesting 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 modulated 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). Leucine may have a protective role in attenuating macrophage foam-cell formation, a hallmark of early atherogenesis, via mechanisms related to the metabolism of cholesterol, triglycerides, and energy production (49).
- Insulin and other antidiabetic medications: Leucine can stimulate insulin secretion and may have additive hypoglycemic effects (8) (43).
- Vitamins B3 and B6: Leucine can interfere with synthesis of these vitamins (9) (10).
- PDE5 inhibitors (sildenafil): Animal models indicate leucine may have synergistic effects (40). Clinical relevance is not known.