- 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 does not improve sugar levels in diabetic patients.
Muscle strength and endurance
Some studies show that leucine improves muscle strength and endurance.
In a clinical 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 the 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. 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 or 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).
In clinical studies, an oral leucine-enriched BCAA mixture increased muscle protein synthesis and reversed sarcopenic processes in cirrhotic patients (24). But supplementation did not have additional effects on exercise capacity, muscle mass or quality of life when compared with supplementation plus exercise (25). Leucine was also found ineffective in improving cerebral blood flow in patients with hepatic encephalopathy (44).
In older adults, taking leucine with daily meals improved integrated myofibrillar protein synthesis in older men, and was equally effective in those with daily protein intake greater than or equal to the RDA (45). A leucine-rich essential amino acid mixture along with exercise significantly improved muscle mass and strength, as well as walking speed in community-dwelling sarcopenic women (26); and leucine-enriched supplements improved sarcopenia in older and older-obese adults (27) (28). In another study, combining resistance training with high-dose supplementation exerted moderate benefits on muscle strength and functional status (29). But according to a systematic review, although supplementation helps improve body weight, body mass index, and lean body mass, it does not enhance muscle strength in older sarcopenia-prone individuals (32). Additional 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). A review concluded that central leucine injection decreases food intake, but this effect was not reproducible with oral leucine (33).
In athletes, dietary supplementation with leucine may improve performance (3) and upper body strength (4). However, randomized trials in younger active populations, one involving resistance training along with powdered leucine/protein shakes (30); and another evaluating a post-surgical rehabilitation program along with supplementation among athletes (31) failed to find improvements attributable to leucine, although it appeared to promote thigh muscle recovery in the latter study (31). Studies in untrained young males reported that supplementation with resistance training does not confer any added benefits in increasing whole-body skeletal muscle mass or strength (46); and does not increase muscle strength or cross-sectional area during resistance training (47)
Preliminary findings suggest that essential amino acids with high levels of leucine may help prevent muscle loss in patients with non small-cell lung cancer (48).
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 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 induces Bcat2 and Bckdha genes during early and late differentiation (35). It was shown to improve insulin sensitivity in mice that were 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 sub-therapeutic 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). Anti-atrophic 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).
- 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). Clinical relevance is not known.