Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n–3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial

Randomized, double-blind, placebo-controlled trial in community-dwelling adults aged 65 years and older at risk of sarcopenia. The active intervention arms each included 38 participants, compared with 31 in the control group, and the study was conducted without structured exercise.

Participants in the active arms received a ready-to-drink, juice-based supplement twice daily for 24 weeks, before breakfast and before the second light meal. The LEU-PRO regimen provided 10.6 g protein and 3.1 g leucine per 200 mL serving, while LEU-PRO+n-3 provided the same protein and leucine plus fish-oil-derived long-chain n-3 PUFAs, including EPA 0.78 g and DHA 1.14 g per serving. The control drink was energy-matched maltodextrin.

Overall, leucine-enriched protein alone and with long-chain n-3 PUFAs did not improve appendicular lean mass, strength, physical performance, or integrated myofibrillar protein synthesis in these well-nourished older adults. Appendicular lean mass was unchanged versus control at postintervention: LEU-PRO 0.01 (-0.20, 0.22), P = 0.93; LEU-PRO+n-3 -0.08 (-0.29, 0.13), P = 0.44. Myofibrillar protein synthesis was also not different from control: LEU-PRO 0.14 %/d (95% CI: -0.25, 0.52; P = 0.46) and LEU-PRO+n-3 0.26 %/d (95% CI: -0.26, 0.78; P = 0.31). Isometric knee flexion peak torque was lower in the LEU-PRO+n-3 group versus control (P < 0.01; d = -0.43), suggesting no additive benefit and a possible adverse effect of the n-3-containing supplement.

The trial was relatively small and lasted only 24 weeks, which may limit power to detect modest changes in muscle outcomes. Participants were generally well nourished, community-dwelling, and recruited from a single center in Ireland, so results may not generalize to more malnourished, frailer, or more diverse populations. Baseline habitual protein intake was already fairly high, which could have reduced the chance of seeing additional benefit from supplementation.