Amino Acid

Leucine

L-leucine

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

3-6

watchEffect Window

Days in disuse studies (often null), weeks to months for functional/body composition endpoints.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Leucine is biologically important for muscle signaling, but isolated supplementation has mixed and often modest real-world outcome effects.

Current clinical evidence suggests leucine alone is not a guaranteed solution for muscle preservation or sarcopenia outcomes. Some benefits appear when leucine is combined with broader nutrition strategies (and sometimes exercise), and special clinical contexts may respond differently. Use leucine as one component of a structured plan with objective outcome tracking.

Essential BCAA with anabolic signaling role. Clinical efficacy depends on context and co-interventions.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Muscle maintenance support (context-dependent)
  • Sarcopenia-related function/body composition (mixed evidence)

Secondary Outcomes

  • Inflammation modulation in critical illness (combined BCAA protocols)
  • Anabolic support when paired with protein feeding

Safety

Contraindications and Interactions

Contraindications

  • BCAA-metabolism disorders
  • Severe renal/hepatic disease without supervision
  • Unsupervised critical-care use

Side effects

  • Nausea
  • Bloating
  • GI discomfort

Interactions

  • Redundant exposure with BCAA/protein blends
  • Coordinate with medically managed protein-restriction plans
  • Co-supplements (vitamin D/protein) may drive observed benefits

Avoid if

  • Inability to monitor objective outcomes
  • Expectation of stand-alone large effect
  • Complex medical status without clinician guidance

Evidence

Study-level References

leucine-SRC-001Double-blind randomized trial
Sourceopen_in_new

Churchward-Venne TA, et al. Leucine supplementation does not attenuate the decline in daily muscle protein synthesis rates or preserve leg muscle mass during leg immobilization in young or older adults: a double-blind randomized trial. Am J Clin Nutr. 2026;123(4):101205. doi:10.1016/j.ajcnut.2026.101205. PMID:41580240

Population: 48 recreationally active adults (young and older)

Dose protocol: 5 g leucine three times daily vs carbohydrate for 3-day unilateral immobilization

Key findings: No preservation of MPS or CSA

Notes: Short duration model

Paper content

No preservation of MPS or CSA

leucine-SRC-002Double-blind randomized controlled trial
Sourceopen_in_new

Chung SX, et al. Efficacy of leucine-rich high protein supplementation on body composition and muscle function among older adults with sarcopenia: a randomized controlled trial. Eur J Nutr. 2026;65(1):17. doi:10.1007/s00394-025-03845-0. PMID:41483327

Population: 47 older adults with/at risk of sarcopenia

Dose protocol: 6 g leucine/day embedded in high-protein supplement for 12 weeks

Key findings: No significant improvement in primary functional/body composition outcomes

Notes: Modest sample, high female proportion

Paper content

No significant improvement in primary functional/body composition outcomes

leucine-SRC-003Multicenter double-blind randomized trial
Sourceopen_in_new

Wulandari Y, et al. High leucine branched-chain amino acids supplementation ameliorates quadriceps femoris muscle thickness reduction and attenuates interleukin-6 in critically ill patients: A randomised controlled trial. Clin Nutr ESPEN. 2025;72:102833. doi:10.1016/j.clnesp.2025.11.153. PMID:41325937

Population: 40 critically ill adults

Dose protocol: 40 g/day BCAA (19 g/day leucine) for 10 days

Key findings: Less muscle-thickness loss and lower IL-6 vs control

Notes: Small sample and combined BCAA intervention

Paper content

Less muscle-thickness loss and lower IL-6 vs control

leucine-SRC-004Systematic review and meta-analysis
Sourceopen_in_new

Guo Y, et al. The Effect of Leucine Supplementation on Sarcopenia-Related Measures in Older Adults: A Systematic Review and Meta-Analysis of 17 Randomized Controlled Trials. Front Nutr. 2022;9:929891. doi:10.3389/fnut.2022.929891. PMID:35845777

Population: 17 RCTs, 1418 older adults

Dose protocol: Isolated and combination leucine interventions

Key findings: Isolated leucine largely null. Combination formulas showed selective benefits

Notes: Heterogeneous interventions and co-supplement use

Paper content

Isolated leucine largely null; combination formulas showed selective benefits

leucine-SRC-006Systematic review and meta-analysis of randomized controlled trials.
Sourceopen_in_new

Xie C, Yan R, Tao R. Combined resistance training and amino acid-based supplementation for sarcopenia in older adults: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2026;27(1):35. doi:10.1186/s12891-025-09436-8. PMID:41540398.

Population: Older adults with sarcopenia across nine randomized controlled trials.

Dose protocol: Meta-analysis of 9 RCTs (n=496) comparing resistance training + amino acid supplementation (EAA, BCAA, leucine, HMB) vs resistance training alone

Key findings: Combination improved handgrip strength (SMD=0.69), gait speed (SMD=0.64), SPPB (SMD=1.69). No significant effect on muscle mass.

Notes: Reinforces that leucine and amino acids enhance function when combined with exercise but do not independently build muscle mass.

Paper content

This systematic review and meta-analysis pooled nine RCTs (n=496) comparing resistance training plus amino acid supplementation (including leucine and derivatives) versus resistance training alone in older adults with sarcopenia. The combination significantly improved handgrip strength (SMD=0.69), gait speed (SMD=0.64), SPPB scores (SMD=1.69), and Five Times Sit-to-Stand performance. However, no significant effect on muscle mass measures was found. The results reinforce the pattern that leucine and related amino acids primarily enhance functional outcomes when combined with exercise, rather than independently improving muscle mass. This is consistent with leucine acting as a signaling molecule that amplifies the training stimulus rather than directly building tissue.

leucine-SRC-005Meta-analysis
Sourceopen_in_new

Huang C, Hsieh MH. Effects of Leucine Supplementation in Older Adults with Sarcopenia: A Meta-Analysis. Nutrients. 2025;17(15):2413. doi:10.3390/nu17152413. PMID:40805998

Population: 10 RCTs plus one prospective study in older sarcopenic adults

Dose protocol: Variable leucine dosages and combinations

Key findings: Limited trend-level improvements, stronger with higher dose/combined interventions

Notes: Reported as low-quality evidence with contradictory findings

Paper content

Limited trend-level improvements, stronger with higher dose/combined interventions

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