Leucine, along with isoleucine and valine, is one of the three branched-chain amino acids (BCAAs). Out of all the amino acids, leucine is the most potent activator of protein synthesis. Cells are able to sense leucine levels, and in response turn on protein synthesis via the enzyme protein mammalian target of rapamycin (mTOR), a master-regulator of protein synthesis.
Given the well-established protein-synthesis activating properties of leucine, a number of human trials have been conducted to determine whether adding supplemental leucine to various protein sources can augment muscle protein synthesis (MPS), particularly in older adults.
Anabolic resistance is a well-established phenomenon during aging, with cells becoming more resistant to turning on protein synthesis. This can be partly ameliorated with extra leucine, as research indicates that older adults need twice as much leucine compared to younger adults for similar activation of MPS.
This increased leucine requirement for MPS in older adults can be partially explained by increased retention of orally ingested leucine in the gut, which is retained twice as much compared to young adults, limiting the amount of leucine that makes it into the blood stream. Resistance to leucine-stimulated protein synthesis also occurs at the cellular level in aging cells.
In a study that compared a low (6 g) dose of whey protein alongside 3 or 5 g of extra leucine to 25 g of whey protein alone in younger adults, the low dose of whey protein plus 5 g of leucine meal stimulated MPS to a similar, but lesser extent than 25 g of whey protein. Another study in younger adults compared the same 25 g dose of whey protein to 6 g of whey protein with an amount of leucine equivalent to 25 g of whey protein and found that only the group that consumed 25 g of whey protein had elevated MPS 3 to 5 hours post-exercise.
Despite the positive effects of leucine on acute rates of MPS, long-term supplementation has largely failed to augment increases in muscle mass and strength in older adults. Further research is needed to determine whether supplementation with leucine can augment muscle mass accretion in older adults with suboptimal protein intake.
Research suggests that supplemental leucine can augment muscle protein synthesis when a suboptimal dose of protein is consumed, but supplemental leucine will not confer additional benefit if a protein bolus sufficient to maximally stimulate muscle protein synthesis is consumed.