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Isoleucine is one of the three branched chain amino acids and appears to promote glucose consumption and uptake. Isoleucine may have roles as an anti-catabolic agent (without promoting synthesis) similar to HMB.

Our evidence-based analysis on isoleucine features 23 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Summary of Isoleucine

Primary information, health benefits, side effects, usage, and other important details

Isoleucine is one of the three branched chain amino acids alongside both leucine and valine. Relative to the other two BCAAs, isoleucine is intermediate for its ability to induce muscle protein synthesis (stronger than valine, but much weaker than leucine) but is able to significantly increase glucose uptake and the usage of glucose during exercise. Isoleucine does not promote glycogen synthesis, however.

Via a PI3K/aPKC dependent mechanism (which is notable since this is neither mediated by the more common AMPK mechanism seen with supplements like berberine nor muscle contraction-mediated uptake) isoleucine can increase glucose uptake into a muscle cell. Leucine also appears to have this ability, but due to leucine stimulating a protein known as S6K (required for protein synthesis) leucine reduces its own efficacy by hindering insulin-stimulated uptake. In other words, while isoleucine and leucine both stimulate glucose uptake leucine then shoots itself in the foot and hinders itself while isoleucine just acts in a predictable and linear manner.

Although extensive human testing has not been conducted yet, isoleucine can be seen as the BCAA which mediates glucose uptake (into a cell) and breakdown (into energy) to a larger degree than other amino acids and may serve a role as a hypoglycemic (in diabetics) or as a performance enhancer (if taken preworkout in a carbohydrate replete state).

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How to Take

Recommended dosage, active amounts, other details

Isoleucine, practically speaking, is likely only a good supplement to purchase when wanting to increase glucose uptake; it is outperformed by leucine for inducing muscle protein synthesis and outperformed by HMB for reducing muscle protein breakdown, yet outperforms both of those agents and valine in increasing glucose uptake into skeletal muscle.

As efficacy has been noted with 0.3-0.45g/kg in rats (the latter being the maximal dose, increasing beyond that does nothing more due to no further absorption) a recommended dosage range for isoleucine per se is 48-72mg/kg (for a 150lb person, 3.3-4.9g).

Isoleucine can be found in branched chain amino acids (in which case, the ratio listed on the label should be investigated and the BCAAs dosed accordingly) and in food products. As isoleucine from food products is also bioactive, supplemental doses of isoleucine taken with meals can be lower (ie. if eating a meal with 50g protein that contains 4g isoleucine already, then a 10.8g dose is no longer needed and 6.8g will suffice).

Study Deep Dives

Click here to see all 23 references.