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

Abstract

Background Leucine-enriched protein (LEU-PRO) and long-chain (LC) n–3 (ω–3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. Objective The impact of LEU-PRO supplementation alone and combined with LC n–3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. Methods This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n–3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n–3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). Results Neither LEU-PRO nor LEU-PRO+n–3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: −7.1 Nm; 95% CI: −12.5, −1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n–3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n–3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n–3 postsupplementation compared with CON (all P < 0.05). Conclusions Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n–3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.

Fish Oil for Healthy Aging: Potential Application to Master Athletes

“…Another possibility is that the participants in the studies reporting no advantageous effects of LC n -3 PUFA supplementation were consuming sufficient protein, precluding the ability to observe an ergogenic effect of LC n -3 PUFA intake. Although most of the LC n -3 PUFA supplementation studies do not report protein intake [ 28 , 47 , 51 ], protein intakes were higher (~ 1.3 g/kg/day) among participants in the study by Murphy et al [ 50 ], which reported no favorable effects of LC n -3 PUFA, compared to ~ 0.9 g/kg/day in the study by Rodacki et al [ 27 ]. Future work that examines how LC n -3 PUFA intake and resistance exercise training influence skeletal muscle mass, strength, and physical performance in older women and men may resolve these discrepancies and provide important information for the field.…”

“…One working hypothesis is that supplementation with LC n -3 PUFAs increases the EPA and DHA content of skeletal muscle potentiating rates of mixed MPS in response to amino acid provision [ 48 , 49 ] leading to increases in skeletal muscle mass and strength [ 27 , 28 , 47 ]. However, both Da Boit et al [ 28 ] and Murphy et al [ 50 ] observed no effect of LC n -3 PUFA supplementation on integrated myofibrillar MPS rates measured over 3–4 days. McGlory et al [ 52 ] also failed to detect an influence of 8 weeks of 3.5 g/day EPA and 0.9 g/day DHA on acute (3 h) rates of myofibrillar MPS in response to oral protein feeding with or without resistance exercise in young men [ 48 , 49 ].…”

“…While there are reports of enhanced rates of MPS, skeletal muscle mass, and strength with LC n -3 PUFA intake in older adults [ 27 , 28 , 47 – 49 ], not all studies have shown a positive effect. Indeed, in a recent study in 107 older adults not engaged in exercise training, consuming 1.6 g/day EPA + 2.3 g/day DHA for 6 months—provided as part of a mixed macronutrient drink containing leucine-enriched protein—failed to impact appendicular lean mass, handgrip strength or knee extensor strength [ 50 ]. Moreover, this intervention [ 50 ] did not improve physical performance in the form of the short performance physical battery (SPPB) and the timed up-and-go test.…”

“…Indeed, in a recent study in 107 older adults not engaged in exercise training, consuming 1.6 g/day EPA + 2.3 g/day DHA for 6 months—provided as part of a mixed macronutrient drink containing leucine-enriched protein—failed to impact appendicular lean mass, handgrip strength or knee extensor strength [ 50 ]. Moreover, this intervention [ 50 ] did not improve physical performance in the form of the short performance physical battery (SPPB) and the timed up-and-go test. Similarly, another study involving over 2000 older adults [ 51 ] did not detect an influence of 3 years of LC n -3 PUFA supplementation (0.3 g EPA/day + 0.7 g DHA/day) alone, or when combined with home-based strength training (30 min × 2 days/week, no load progression), on the primary outcome of SPPB test score.…”

Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia

“…It is understood that low-protein intake may be a risk factor for sarcopenia since a greater amount of protein are required to stimulate MPS in the elderly ( 8 , 12 ). However, many human dietary intervention studies have shown little or no impact of protein ( 22 , 23 ), leucine ( 24 – 26 ), or IAA ( 27 ) supplementation on muscle mass and/or strength in non-exercising older adults. Therefore, resistance exercise, regulation of other nutrient sensors that modulate MPS aside from AA, and/or even greater amounts of protein supplementation/intake than those offered in this study may be essential tools to fight sarcopenia in healthy older adults.…”