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⁾.