Protein Ingestion to Stimulate Myofibrillar Protein Synthesis Requires Greater Relative Protein Intakes in Healthy Older Versus Younger Men

Moore, Daniel R.; Churchward-Venne, Tyler A.; Witard, Oliver; Breen, Leigh; Burd, Nicholas A.; Tipton, Kevin D.; Phillips, Stuart M.

doi:10.1093/gerona/glu103

Cited by 770Muscle metabolism and nutritionNutrition and Health in AgingMuscle Physiology and Disorders

Protein Ingestion to Stimulate Myofibrillar Protein Synthesis Requires Greater Relative Protein Intakes in Healthy Older Versus Younger Men

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Moore, Daniel R., Churchward-Venne, Tyler A., Witard, Oliver, Breen, Leigh, Burd, Nicholas A., Tipton, Kevin D., Phillips, Stuart M.·2015·The Journals of Gerontology: Series A

DOI 10.1093/gerona/glu103

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Abstract

Background.: Adequate protein ingestion-mediated stimulation of myofibrillar protein synthesis (MPS) is required to maintain skeletal muscle mass. It is currently unknown what per meal protein intake is required to maximally stimulate the response in older men and whether it differs from that of younger men. Methods.: We retrospectively analyzed data from our laboratories that measured MPS in healthy older (~71 years) and younger (~22 years) men by primed constant infusion of l-ring-[13C6]phenylalanine after ingestion of varying amounts (0–40 g) of high-quality dietary protein as a single bolus and normalized to body mass and, where available, lean body mass (LBM). Results.: There was no difference (p = .53) in basal MPS rates between older (0.027±0.04%/h; means ± 95% CI) and young (0.028 ± 0.03%/h) men. Biphase linear regression and breakpoint analysis revealed the slope of first line segment was lower (p < .05) in older men and that MPS reached a plateau after ingestion of 0.40 ± 0.19 and 0.24 ± 0.06 g/kg body mass (p= .055) and 0.60 ± 0.29 and 0.25 ± 0.13 g/kg lean body mass (p < .01) in older and younger men, respectively. Conclusions.: This is the first report of the relative (to body weight) protein ingested dose response of MPS in younger and older men. Our data suggest that healthy older men are less sensitive to low protein intakes and require a greater relative protein intake, in a single meal, than young men to maximally stimulate postprandial rates of MPS. These results should be considered when developing nutritional solutions to maximize MPS for the maintenance or enhancement of muscle mass with advancing age.

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Older muscle may be slower to respond and less sensitive to protein ingestion, typically requiring 40 g doses to robustly stimulate muscle protein synthesis.
“Recent reports suggest that older muscle may be slower to respond and less sensitive to protein ingestion, typically requiring 40 g doses to robustly stimulate muscle protein synthesis [84–86].”
From ISSN exercise & sports nutrition review update: research & recommendations (2018) · cites this paper as [86]
The Discussion reports reduced sensitivity of older men's muscle to ingested protein, and the Results estimate that myofibrillar protein synthesis plateaus at about 0.40 g/kg body mass. The paper does not establish that older muscle responds more slowly or that a fixed 40 g dose is typically required; 40 g was the upper end of the doses studied. (LLM, conf=0.89)
Experimental — accuracy not yet measured
MPS shows a saturable dose-response relationship with increasing protein intake.
“we recognised that the process of muscle protein synthesis (MPS), as the primary determinant of muscle hypertrophy,13 shows a saturable dose-response relationship with increasing protein intake.14”
From A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults (2018) · cites this paper as [14]
Older individuals require higher per-meal protein doses to achieve similar rates of muscle protein synthesis compared with younger participants.
“Older individuals are anabolically resistant74 and require higher per-meal protein doses to achieve similar rates of MPS, the primary variable regulating changes in skeletal muscle mass,75 compared with younger participants.14”
From A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults (2018) · cites this paper as [14]
Four covariates were chosen a priori to be included in the meta-regression.
“Four covariates were chosen a priori to be included in our meta-regression: baseline protein intake (g/kg/day), postexercise protein dose (g), chronological age and training status because there is evidence that baseline protein intake,66 protein dose,14 age67 and training status68 could influence the efficacy of protein supplementation; summarised here.4 5”
From A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults (2018) · cites this paper as [14]
A recent retrospective analysis showed a breakpoint for the stimulation of muscle protein synthesis when ingesting an isolated protein source at 0.24 g protein/kg in younger participants and 0.40 g protein/kg in older participants.
“A recent retrospective analysis showed a ‘breakpoint’ for the stimulation of MPS when ingesting an isolated protein source at 0.24 g protein/kg and 0.40 g protein/kg in younger and older participants, respectively.14”
From A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults (2018) · cites this paper as [14]

Compared with an optimal dose per meal of 0.24 g/kg in young men, a dose of 0.4 g/kg is required to optimize muscle protein synthesis in older men, which equals 1.2 g/kg/day when translated over three meals per day.
“work from Moore et al. (2015) found that compared with an optimal dose per meal of 0.24 g kg -1 in young men, a dose of 0.4 g kg -1 is required to optimize muscle protein synthesis in older men, which equals 1.2 g kg -1 day -1 when translated over three meals per day.”
From Sex‐based differences in endurance exercise muscle metabolism: impact on exercise and nutritional strategies to optimize health and performance in women (2016) · cites this paper as Moore et al. 2015
The pronounced increase in leg lean mass and lean body mass with whey protein supplementation supports raising protein intake in older adults to overcome the age-related heightened anabolic resistance to protein feeding.
“The pronounced increase in LLM and LBM with WP supplementation provides support for increasing protein intake in older adults in an effort to overcome the heighted anabolic resistance to protein feeding that occurs with age (38).”
From A randomized controlled trial of the impact of protein supplementation on leg lean mass and integrated muscle protein synthesis during inactivity and energy restriction in older persons (2018) · cites this paper as [38]
Previous research has shown that daily whey protein supplementation at a dose considered suboptimal for older adults is ineffective at reducing skeletal muscle loss during immobilization.
“Previously, daily supplementation with WP, albeit at what we would consider a suboptimal dose for an older adult population (38), has been shown to be ineffective at reducing losses in skeletal muscle with immobilization (15).”
From A randomized controlled trial of the impact of protein supplementation on leg lean mass and integrated muscle protein synthesis during inactivity and energy restriction in older persons (2018) · cites this paper as [38]
The current recommended dietary allowance for protein at 0.8 g/kg/day may be insufficient for older adults due to their inability to absorb and utilize protein to the same extent as younger individuals.
“The current RDA for protein at 0.8 g/kg/day may be insufficient for older adults due to their inability to absorb and utilize protein to the same extent compared to younger individuals [106,108,130].”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [130]
The optimal dose of protein post exercise in healthy young men may be best quantified in a g/kg basis or g/kg lean mass basis, with approximately 0.25 g/kg body mass and 0.25 g/kg lean mass appearing to elicit maximum rates of MPS.
“This retrospective analysis has suggested that the optimal dose of protein post exercise in healthy young men may be best quantified in a g/kg basis or even a g/kg lean mass basis with ~0.25 g/kg body mass and 0.25 g/kg lean mass appearing to elicit the maximum rates of MPS [109].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [109]
The fractional synthetic rate is lower in healthy elderly individuals compared with young peers.
“despite the lower fractional synthetic rate in healthy elderly individuals compared with young peers [78,79,80]”
From Effects of Protein Supplementation Combined with Exercise Intervention on Frailty Indices, Body Composition, and Physical Function in Frail Older Adults (2018) · cites this paper as [79]

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Authors: Moore, D. R., Churchward-Venne, T. A., Witard, O., Breen, L., Burd, N. A., Tipton, K. D., & Phillips, S. M.
Affiliations: University of Toronto (CA)
2 Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
University of Stirling (GB)
University of Birmingham (GB)
University of Illinois Urbana-Champaign (US)
McMaster University (CA)
Corresponding author: Phillips, Stuart M.
ORCID: Moore, Daniel R.
Witard, Oliver
Breen, Leigh
Burd, Nicholas A.
Tipton, Kevin D.
Phillips, Stuart M.
Venue: The Journals of Gerontology: Series A
Publisher: Oxford University Press (OUP)
Published: 2014-07-23
Volume: 70
Issue: 1
Pages: 57-62
ISSN: 1079-5006 (ISSN-L)
1758-535X
DOI: 10.1093/gerona/glu103
OpenAlex: W2099210995
Cited by: 770
References: 40
Citations by year: 2026: 58 · 2025: 61 · 2024: 56 · 2023: 59 · 2022: 67 · 2021: 94 · 2020: 91 · 2019: 70 · 2018: 69 · 2017: 61 · 2016: 47 · 2015: 30 · 2014: 6 · 2013: 1
FWCI: 23.90
Type: journal article
Language: en
Open access: green
durham-repository.worktribe.com
Licence: cc-by
Locations: The Journals of Gerontology Series A (publishedVersion)
PubMed (publishedVersion)
Durham Research Online (Durham University) (acceptedVersion)
Durham Research Online (Durham University) (submittedVersion, cc-by)
Research Portal (King's College London) (submittedVersion, other-oa)
Stirling Online Research Repository (University of Stirling) (submittedVersion, public-domain)
Funders: Nestec
Natural Sciences and Engineering Research Council of Canada
Medical Research Council (MR/K00414X/1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: myofibrillar protein synthesis, protein intake, older men, age-related muscle loss, skeletal muscle mass, dose-response relationship, lean body mass, dietary protein, muscle protein synthesis
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Aging, Body Weight, Dietary Proteins, Eating, Humans, Male, Muscle Proteins, Myofibrils, Nutritional Requirements, Organ Size, Retrospective Studies, Body Mass Index, Muscle, Skeletal, Young Adult, Sarcopenia

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Protein Ingestion to Stimulate Myofibrillar Protein Synthesis Requires Greater Relative Protein Intakes in Healthy Older Versus Younger Men

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