The leucine trigger hypothesis: Debunked? Original paper

In this meta-analysis of randomized controlled trials, higher intakes of leucine around the time of resistance exercise were strongly associated with higher postexercise muscle protein synthesis rates in older adults, but not younger adults.

The relationship between ingested leucine and the magnitude of postprandial (postmeal) muscle protein synthesis (MPS) rates after exercise.

MPS rates were assessed 1.5–6 hours after resistance exercise and protein ingestion. The researchers also assessed whether the peak plasma leucine level, rate of rise to peak plasma leucine level, and the incremental area under the curve for total postprandial plasma leucine availability were associated with MPS rates.

A total of 697 adults (79% men, 21% women) without apparent health conditions.

A meta-analysis of 38 randomized controlled trials was performed. For inclusion, the trials had to report MPS rates after ingestion of an amino acid, amino acid mixture, isolated protein source, protein-containing whole food, or mixed meal within an hour (before or after) of performing resistance exercise.

The vast majority of trials used whey protein as the protein source, whereas a few trials used casein, milk protein concentrate, or crystalline essential amino acid mixtures; 2 trials used beef; 2 trials used mycoprotein, and 1 trial each used pork, cheese, mealworms, collagen protein, potato protein, egg white, and egg yolk.

Separate analyses were performed for studies that included younger adults (average age range of 19–29) and older adults (average age range of 57–74).

There was no association between the dose of leucine and postexercise MPS rates in younger adults, whereas higher doses of leucine were associated with higher MPS rates in older adults at up to 6 grams of leucine (the highest amount consumed).

There was no association between the peak plasma leucine level, the rate of rise to peak plasma leucine level, or the total postprandial plasma leucine availability incremental area under the curve and MPS rates.

The leucine trigger hypothesis states that the amount of leucine within a meal dictates the rate of MPS after ingestion and that 2–3 grams of leucine is sufficient to maximize the MPS response.^[1][2]

The authors reported that, based on prior evidence,^[2] the leucine trigger hypothesis may only apply to protein isolates consumed on their own (i.e., without the presence of other foods and nutrients). This might at least partially explain the contrasting findings between younger and older adults because all of the studies in older adults used protein isolates.