Amino Acid

Isoleucine

L-Isoleucine

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

30 g/day in oral HE protocol

watchEffect Window

Acute (hours-to-days) to long-term (months) depending on endpoint

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Isoleucine is a branched-chain amino acid with disease-context evidence in cirrhosis, but little reason for standalone supplementation in healthy people.

Evidence is context dependent. Trials most often evaluate exercise outcomes such as fatigue, blood flow, or muscle soreness, and some show small benefits at adequate doses. Minority uses include support for wound healing, immune function, and sleep quality. Effects vary with baseline protein intake, training status, and coingested nutrients.

A disease-context amino-acid intervention signal in cirrhosis: may support neurologic/hepatic protein handling, with weak evidence for healthy-user performance benefits.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • In HE, 10 g ×3/day isoleucine improved perfusion and HE trajectory versus leucine (PMID:30013913).
  • IV isoleucine improved protein balance in cirrhotic stress simulation (PMID:17326149).

Secondary Outcomes

  • Mixed BCAA (with isoleucine) improved insomnia outcomes in TBI pilot (PMID:35602971).
  • BCAA did not outperform whey in cirrhosis strength outcomes over 12 months (PMID:38404263).

Safety

Contraindications and Interactions

Contraindications

  • Unstable decompensated cirrhosis
  • Known amino acid metabolism disorders
  • Severe renal/hepatic instability without specialist management

Side effects

  • Mild GI/taste intolerance
  • Potential adherence burden from long-term amino-acid dosing

Interactions

  • HE and hepatic regimens
  • Co-administered amino-acid formulas

Avoid if

  • Clinical decompensation without close monitoring
  • Severe neurologic deterioration
  • Unsure diagnosis with fluctuating HE

Evidence

Study-level References

isoleucine-SRC-001Randomized double-blind clinical trial
Sourceopen_in_new

Romeiro et al. *Neuroimage Clinical*. 2018;19:302-310. PMID:30013913.

Population: 27 adults with cirrhosis and HE

Dose protocol: 10 g isoleucine or leucine packet, 3 times/day for 12 months

Key findings: Improved perfusion and HE-related clinical trajectory in isoleucine arm.

Notes: Small sample and constrained design. Still a relevant disease-specific signal.

Paper content

Improved perfusion and HE-related clinical trajectory in isoleucine arm.

isoleucine-SRC-002Randomized crossover intervention
Sourceopen_in_new

Olde Damink SWM et al. *Hepatology*. 2007;45(3):560-568. PMID:17326149.

Population: 16 cirrhotic patients in simulated upper GI bleed setting

Dose protocol: IV isoleucine vs saline during catabolic stress protocol

Key findings: Improved net hepatic and skeletal protein kinetics with isoleucine.

Notes: Specialized small inpatient model. Limited external generalizability.

Paper content

Improved net hepatic and skeletal protein kinetics with isoleucine.

isoleucine-SRC-003Randomized double-blind pilot trial
Sourceopen_in_new

Elliott JE et al. *Front Syst Neurosci*. 2022;16:854874. PMID:35602971.

Population: Veterans with TBI

Dose protocol: 30 g/day BCAA for 21 days (mixed blend)

Key findings: Directional sleep improvements versus placebo arms.

Notes: Mixed formula, short duration, no isolated amino-acid inference.

Paper content

Directional sleep improvements versus placebo arms.

isoleucine-SRC-004Randomized controlled trial
Sourceopen_in_new

Chronic BCAA vs whey protein randomized trial in cirrhosis (PMID:38404263).

Population: Adults with cirrhosis and reduced strength

Dose protocol: 30 g/day BCAA vs whey control for 12 months

Key findings: No significant difference in grip strength or lean mass versus control.

Notes: Long duration but no clear superiority for protein functional endpoints.

Paper content

No significant difference in grip strength or lean mass versus control.

isoleucine-SRC-005Structured review context
Sourceopen_in_new

Mechanistic and review synthesis in HE/ammonia literature (PMID:21636533; additional mixed BCAA literature).

Population: Cirrhosis/HE/metabolic studies

Dose protocol: Heterogeneous BCAA intervention designs

Key findings: Mixed signal for ammonia and hard clinical outcomes across cohorts.

Notes: Indirectness when inferring isolated isoleucine effects.

Paper content

Mixed signal for ammonia and hard clinical outcomes across cohorts.

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