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Personalized Protein Supplementation Improves Total Protein, Leucine, and Energy Intake in (Pre)Sarcopenic Community-Dwelling Older Adults in the ENHANce RCT.

ABSTRACT: Recommendations concerning protein quantity, source, and leucine intake for older adults are difficult to reach by regular dietary intake. This randomized clinical trial assesses in sarcopenic community-dwelling older adults (i) the regular (non-supplemented) daily protein and leucine intake; and (ii) the effect of personalized protein supplementation (aiming for an evenly distributed total protein intake of 1.5 g·kg^-1·d^-1 of body mass, accounting for energy intake) on regular and total (dietary and supplemental) intake. A preliminary feasibility study in participants of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study was performed with the objective to assess the intake and distribution of regular dietary protein and leucine, protein source and energy intake in (pre)sarcopenic community-dwelling older adults. Moreover, this study aimed to assess if personalized protein supplementation was feasible without negatively affecting regular dietary intake. ENHANce (NCT03649698) is a 5-armed RCT that assesses the effect of anabolic interventions on physical performance in (pre)sarcopenic older adults. In August 2019, n = 51 participants were included in ENHANce with complete available data on dietary intake at screening and thus eligible for inclusion in present analysis. Of these, n = 35 participants completed the intervention period of ENHANce at the moment of analysis, allowing an exploration of the effect of supplementation on regular dietary intake. The regular dietary protein intake of 51 (pre)sarcopenic adults (73.6 ± 6.5 years) was 1.06 ± 0.3 g·kg^-1·d^-1 of body mass. Protein supplementation (n = 20) improved total protein intake to 1.55 ± 0.3 g·kg^-1·d^-1 of body mass (P < 0.001) without affecting regular dietary protein (P = 0.176) or energy intake (P = 0.167). Placebo supplementation (n = 15) did not affect regular dietary protein intake (P = 0.910) but decreased regular dietary energy intake (P = 0.047). Regular leucine intake was unevenly distributed over the day, but increased by supplementation at breakfast (P < 0.001) and dinner (P = 0.010) to at least 2.46 g leucine·meal^-1, without reducing regular dietary leucine intake (P = 0.103). Animal-based protein intake-the main protein source-was not affected by supplementation (P = 0.358). Personalized protein supplementation ensured an adequate quantity and even distribution of protein and leucine over the day, without affecting regular dietary protein or energy intake.

SUBMITTER: Dedeyne L

PROVIDER: S-EPMC8381276 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRapid growth of skeletal muscle in the neonate requires the coordination of protein deposition and myonuclear accretion. During this developmental stage, muscle protein synthesis is highly sensitive to amino acid supply, especially Leu, but we do not know if this is true for satellite cells, the source of muscle fiber myonuclei.ObjectiveWe examined whether dietary protein restriction reduces myonuclear accretion in the neonatal pig, and if any reduction in myonuclear accretion is mitigated by restoring Leu intake.MethodsNeonatal pigs (1.53 ± 0.2 kg) were fitted with jugular vein and gastric catheters and fed 1 of 3 isoenergetic milk replacers every 4 h for 21 d: high protein [HP; 22.5 g protein/(kg/d); n= 8]; restricted protein [RP; 11.2 g protein/(kg/d); n= 10]; or restricted protein with Leu [RPL; 12.0 g protein/(kg/d); n= 10]. Pigs were administered 5-bromo-2'-deoxyuridine (BrdU; 15 mg/kg) intravenously every 12 h from days 6 to 8. Blood was sampled on days 6 and 21 to measure plasma Leu concentrations. On day 21, pigs were killed and the longissimus dorsi (LD) muscle was collected to measure cell morphometry, satellite cell abundance, myonuclear accretion, and insulin-like growth factor (IGF) system expression.ResultsCompared with HP pigs, postprandial plasma Leu concentration in RP pigs was 37% and 47% lower on days 6 and 21, respectively (P < 0.05); Leu supplementation in RPL pigs restored postprandial Leu to HP concentrations. Dietary protein restriction reduced LD myofiber cross-sectional area by 21%, satellite cell abundance by 35%, and BrdU+ myonuclear abundance by 25% (P < 0.05); Leu did not reverse these outcomes. Dietary protein restriction reduced LD muscle IGF2 expression by 60%, but not IGF1 or IGF1R expression (P < 0.05); Leu did not rescue IGF2 expression.ConclusionsSatellite cell abundance and myonuclear accretion in neonatal pigs are compromised when dietary protein intake is restricted and are not restored with Leu supplementation.

Project description:BackgroundProtein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition.Methodology/principal findingsMale Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in the MC-L and MC-H groups than in the MC-CON group.Conclusion/significanceOur data are the first to demonstrate that long-term supplementation with leucine improved acquired growth hormone resistance in rats with protein-energy malnutrition. Leucine might promote skeletal muscle protein synthesis by regulating downstream anabolic signaling transduction.

Project description:PurposeTo examine the cost effectiveness of dietary advice to increase protein intake on 6-month change in physical functioning among older adults.MethodsIn this multicenter randomized controlled trial, 276 community-dwelling older adults with a habitual protein intake < 1.0 g/kg adjusted body weight (aBW)/d were randomly assigned to either Intervention 1; advice to increase protein intake to ≥ 1.2 g/kg aBW/d (PROT, n = 96), Intervention 2; similar advice and in addition advice to consume protein (en)rich(ed) foods within half an hour after usual physical activity (PROT + TIMING, n = 89), or continue the habitual diet with no advice (CON, n = 91). Primary outcome was 6-month change in 400-m walk time. Secondary outcomes were 6-month change in physical performance, leg extension strength, grip strength, body composition, self-reported mobility limitations and quality of life. We evaluated cost effectiveness from a societal perspective.ResultsCompared to CON, a positive effect on walk time was observed for PROT; - 12.4 s (95%CI, - 21.8 to - 2.9), and for PROT + TIMING; - 4.9 s (95%CI, - 14.5 to 4.7). Leg extension strength significantly increased in PROT (+ 32.6 N (95%CI, 10.6-54.5)) and PROT + TIMING (+ 24.3 N (95%CI, 0.2-48.5)) compared to CON. No significant intervention effects were observed for the other secondary outcomes. From a societal perspective, PROT was cost effective compared to CON.ConclusionDietary advice to increase protein intake to ≥ 1.2 g/kg aBW/d improved 400-m walk time and leg strength among older adults with a lower habitual protein intake. From a societal perspective, PROT was considered cost-effective compared to CON. These findings support the need for re-evaluating the protein RDA of 0.8 g/kg BW/d for older adults.Trial registrationThe trial has been registered at ClinicalTrials.gov (NCT03712306). Date of registration: October 2018. Registry name: The (Cost) Effectiveness of Increasing Protein Intake on Physical Functioning in Older Adults. Trial Identifier: NCT03712306.

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Personalized Protein Supplementation Improves Total Protein, Leucine, and Energy Intake in (Pre)Sarcopenic Community-Dwelling Older Adults in the ENHANce RCT.

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