Adding free leucine to a balanced essential amino acid mixture suppresses intracellular transamination of isoleucine and valine in healthy older adults.

BACKGROUND

Adding leucine (LEU) to protein meals enhances protein anabolism, but excess LEU reduces valine (VAL) and isoleucine (ILE) plasma concentrations. We examined in older adults whether additional LEU added to an essential amino acid (EAA) mixture reduces the intracellular catabolism of VAL and ILE, and their keto acids ɑ-ketoisovaleric acid (KIV)and 2-keto-3-methyl-pentanoate (KMV).

METHODS

Using a randomized placebo-controlled crossover design, 11 older adults (60-80 years) consumed 20g EAA, 20g EAA+3g LEU (EAA + LEU), and water (baseline) on separate study days. A pulse of stable isotopes containing LEU, VAL, ILE, ɑ-ketoisocaproic acid (KIC), KMV, and KIV was administered IV to assess their whole-body and compartmental kinetics. Blood samples were taken, and enrichments analyzed using LC/GS-MS/MS. Data are expressed as percentage change after intake of EAA + LEU vs EAA [95%CI].

RESULTS

Plasma concentrations of LEU (55% [40%, 71%]; p < 0.001) and KIC (38% [26%, 51%]; p < 0.001) increased more after EAA + LEU than after EAA intake (both p < 0.0001) while ILE (-16% [-25%, -6%]; p = 0.001), KMV (-22% [-30%, -14%]; p < 0.001), and KIV (-21% [-29%, -13%]; p < 0.001) concentrations decreased. Intracellular disposal of LEU (43% [30%, 56%]; p < 0.001) and KIC (28% [4%, 52%]; p = 0.006) increased more after EAA + LEU mixture intake (LEU p < 0.0001, KIC p = 0.020), but those of ILE and VAL did not change. The intracellular pool sizes of KMV (19% [-35%, -4%],p = 0.019) and KIV (-25% [-43%, -7%]; p = 0.019) decreased.

CONCLUSIONS

In older adults, adding LEU to an EAA mixture suppresses intracellular catabolism of the other BCAAs and their keto acids, possibly negatively affecting anaplerotic flux into the tricarboxylic acid cycle and thus muscle health.

CLINICAL TRIAL REGISTRY: Trial registration ClinicalTrials.gov: NCT05400733.