Benefits
Muscle protein synthesis activation
In healthy older women, a 15 g protein drink with 4.2 g of leucine raised muscle protein synthesis more than a drink with the same protein and 1.3 g of leucine, at rest and after leg exercise. In a second trial, 10 g of protein with added leucine (3 g in total) matched 25 g of whey isolate with the same leucine. These are short-term synthesis measurements over days, not measured muscle growth or strength.
Lean body mass in older adults
A meta-analysis of 16 studies in 999 older adults found leucine-rich protein supplements increased lean body mass by about 1 kg versus control (95% CI 0.43 to 1.55 kg), more in people who already had low muscle mass, with no significant effect on strength. In a separate 3-month trial, free leucine alone (7.5 g a day) did not change muscle mass or strength in healthy older men.
Mechanism of action
Direct mTORC1 activation via Sestrin2-GATOR2 pathway
In cell and animal research, leucine binds Sestrin2, releasing its hold on the GATOR2 complex. This activates Rag GTPases that bring mTORC1 to the lysosome, where Rheb switches it on. mTORC1 then phosphorylates S6K1 and 4E-BP1, starting translation of muscle proteins. This is the molecular basis of the leucine trigger idea.
Insulin secretagogue activity
Leucine stimulates insulin release from pancreatic beta cells through glutamate dehydrogenase activation and ATP production, a route that does not depend on glucose sensing. This is worked out mainly from laboratory research, and none of the human trials cited on this page measured insulin, blood sugar or amino acid uptake.
mTOR-independent protein synthesis via eIF4F complex
Beyond mTOR, leucine helps assemble the eIF4F translation initiation complex by freeing eIF4E from 4E-BP1, which lets ribosomes attach to muscle protein messages. This pathway is described from laboratory work on cells and tissue, and how much it matters for people taking leucine supplements was not tested in the studies cited here.
Clinical trials
Randomized parallel-group trial: twice-daily 15 g milk protein drink with 4.2 g of leucine versus 15 g mixed milk and soy protein drink with 1.3 g of leucine, on a fixed diet with 1.0 g/kg/day of protein; one leg did resistance exercise. (Devries et al. 2018, Am J Clin Nutr)
22 healthy women aged 65 to 75 (11 per group).
Hourly muscle protein synthesis after feeding rose more with the high-leucine drink (rested leg 53 vs 13 percent; exercised leg 87 vs 30 percent). Over the supplement days, synthesis rose in both legs with high leucine but only in the exercised leg with the control drink. Short-term synthesis rates only, not muscle growth or strength. Co-authors worked for PepsiCo R&D Nutrition.
Single-blind randomized parallel-group trial: twice-daily 10 g milk protein with added leucine (3 g leucine in total) versus 25 g whey protein isolate (3 g leucine) for 6 days; one leg did resistance exercise. Co-authors worked for PepsiCo R&D Nutrition. (Devries et al. 2018, J Nutr)
22 healthy women aged about 69 (11 per group).
Both drinks raised hourly muscle protein synthesis, with a larger rise from the leucine drink in the exercised leg only, and both raised daily synthesis in the exercised leg by 9 percent. The authors concluded the lower-protein, leucine-matched drink gave similar results and that longer trials are needed. Synthesis rates only.
Systematic review and meta-analysis of randomized or crossover trials of leucine-rich protein supplements in older adults, looking at body measurements and muscle strength. (Komar et al. 2015, J Nutr Health Aging)
999 older adults across 16 studies.
Leucine-rich supplementation increased lean body mass by 0.99 kg versus control (95% CI 0.43 to 1.55, p=0.0005), more in people who already had low muscle mass, while handgrip and knee extension strength did not differ significantly from control. The trials were heterogeneous, and results in older adults may not apply to younger or athletic users.
Randomized placebo-controlled trial of 2.5 g of free leucine or placebo with each main meal (7.5 g a day) for 3 months, measuring muscle mass by CT and DXA, one-rep max strength, insulin sensitivity and blood lipids. (Verhoeven et al. 2009, Am J Clin Nutr)
30 healthy men aged about 71 (15 per group).
Null result. Muscle mass and strength did not change in either group, and insulin sensitivity, HbA1c and blood lipids did not improve. The authors concluded that long-term free leucine does not augment muscle mass or strength in healthy older men.