Supplement
Isoleucine is an essential amino acid, one the body cannot make, that cells use to build proteins and handle energy. People mostly look at it for blood sugar, and the evidence is limited: across several rodent studies, blood glucose fell by about 20% as muscle tissue took up more sugar. Nearly all of this came from animal or lab work, so it is still unclear whether people would see the same effect.
Sources: PMID 14651987; PMID 16140883
- Updated
- How we grade
- 12 studies cited
- Best evidence
- Grade C
- Conditions studied
- 1
- Outcomes
- 4
- Graded outcomes
- 0013
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Blood Glucose (Acute Reduction) In multiple rodent studies, acute isoleucine administration reduced plasma glucose by ~20% via increased skeletal muscle glucose uptake (up to 73% above controls), enhanced glucose oxidation, and suppressed hepatic gluconeogenesis through a PI3K-dependent, insulin-independent mechanism (Doi et al. 2003, 2005, 2007). A porcine study confirmed upregulation of GLUT1 and GLUT4 transporters (Zhang et al. 2016). However, chronic supplementation impaired glucose tolerance in lean mice (O'Rielly et al. 2020), and no human trials have validated these acute effects. | Improves (the measure goes down) | Moderate effect | 7 studies | |||
Studies that measured blood glucose (acute reduction)
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| Innate Immune Function (Beta-Defensin Induction) L-isoleucine stereospecifically induces beta-defensin expression in epithelial cells via NF-kB signaling (Fehlbaum et al. 2000). In mice with active tuberculosis, intratracheal isoleucine upregulated beta-defensins 3 and 4, reducing bacterial loads in both drug-sensitive and MDR strains (Rivas-Santiago et al. 2011). A small pediatric RCT (n=50) of isoleucine-supplemented ORS showed non-significant increases in beta-defensin levels (Alam et al. 2011). | Improves (the measure goes up) | Small effect | 6 studies | 50 people | ||
Studies that measured innate immune function (beta-defensin induction)
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| Muscle Protein Synthesis Isoleucine independently activates mTOR and S6K1 phosphorylation in bovine mammary cell culture (Appuhamy et al. 2012), but BCAAs alone are insufficient to stimulate net muscle protein synthesis in humans due to the requirement for all essential amino acids (Wolfe 2017 review). High-dose isoleucine may compete with leucine for shared intestinal and muscle transporters, potentially blunting leucine's anabolic effect (Santos & Nascimento 2019). | Improves (the measure goes up) | Small effect | 3 studies | |||
Studies that measured muscle protein synthesis
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| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Diarrhea Severity (Pediatric Acute) A single double-blind RCT in 50 children (aged 6-36 months) with acute watery diarrhea found that L-isoleucine (2 g/L) added to oral rehydration salts significantly reduced stool output on day 3 (p=0.035) and ORS intake on day 1 (p=0.04), though cumulative stool reduction (26%) and diarrhea duration did not reach statistical significance (Alam et al. 2011). | Improves (the measure goes down) | Small effect | 3 studies | 50 people | ||
Studies that measured diarrhea severity (pediatric acute)
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Key findings
- Blood Glucose (Acute Reduction)Improves (the measure goes down)
- Innate Immune Function (Beta-Defensin Induction)Improves (the measure goes up)
- Diarrhea Severity (Pediatric Acute)Improves (the measure goes down)
Studies cited
12 studies from PubMed
- Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.
- The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine
- The Effect of Isoleucine Supplementation on Body Weight Gain and Blood Glucose Response in Lean and Obese Mice.
- Isoleucine plays an important role in the growth, immune function, protein metabolism, fatty acid metabolism, and glucose transport of animals
- Effects of isoleucine on glucose uptake through the enhancement of muscular membrane concentrations of GLUT1 and GLUT4 and intestinal membrane concentrations of Na+/glucose co-transporter 1 (SGLT-1) and GLUT2.
- Isoleucine and leucine independently regulate mTOR signaling and protein synthesis in MAC-T cells and bovine mammary tissue slices
- Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis.
- L-isoleucine-supplemented oral rehydration solution in the treatment of acute diarrhoea in children: a randomized controlled trial.
- Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis
- Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity
- Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes
- An essential amino acid induces epithelial beta-defensin expression