Metabolic flexibility following resistance exercise and a high protein diet in older men: results from a 12-week randomized controlled trial

Corbin Griffen; Derek Renshaw; Michael Duncan; Alexander Dallaway; Hapal Randeva; Martin O Weickert; John Hattersley

doi:10.1016/j.exger.2026.113101

Metabolic flexibility following resistance exercise and a high protein diet in older men: results from a 12-week randomized controlled trial

Corbin Griffen
, Derek Renshaw
, Michael Duncan
, Alexander Dallaway
, Hapal Randeva
, Martin O Weickert
, John Hattersley

University Hospitals Coventry and Warwickshire NHS Trust
University of Roehampton
Victoria University of Wellington
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism
University of Warwick

Research output: Contribution to journal › Article › peer-review

4 Downloads (Pure)

Abstract

Purpose: Aging and sarcopenia are associated with metabolic inflexibility. This study investigated the effects of resistance exercise (RE) and a high protein diet (PRO) on metabolic flexibility (the ability to adjust rates of substrate oxidation to changes in fuel availability) in older men.MethodsIn a pooled groups analysis, 33 healthy older men [(mean±SE) age: 67±1 years; BMI: 25.4±0.4 kg/m2] were randomized to either RE (2×/week; n=17) or no exercise (NE; n=16), and either high protein diet [∼1.6 g/kg/day (∼25% of energy intake (EI))] via twice daily (25 g) whey protein supplementation (PRO; n=17) or control (CON, 2 × 23.75 g maltodextrin/day; n=16). An exploratory sub-analysis was also conducted between RE+CON (n=8) and RE+PRO (n=9). At baseline and 12 weeks, participants resided in whole-room indirect calorimeters for 24 h for measurement of metabolic flexibility via changes in relative substrate utilization [non-protein respiratory quotient (npRQ)] under different conditions (fasting sleep to awake, step exercise, and 2-h postprandial meal consumption, and peak step exercise to exercise end).ResultsCompared to NE, RE significantly increased (indicating medium-to-large effects on improved metabolic flexibility) ΔnpRQ (awake-sleep) (+0.02±0.004 vs. 0.00±0.05, p=0.01, f=0.48), and ΔnpRQ (steady state exercise-sleep) (p ≤0.045) and ΔnpRQ (peak exercise-exercise end) (p ≤0.04, f=0.39–0.64) for two step exercise bouts performed ∼2 h postprandially. Compared to CON, PRO increased ΔnpRQ (steady state-sleep) for one step exercise bout (+0.02±0.01 vs. -0.002±0.01, p=0.047, f=0.39). No significant differences occurred between the RE+CON and RE+PRO groups (p ≥0.06).ConclusionIn older men, RE improved metabolic flexibility. PRO had a limited benefit. No synergistic effects were observed.

Original language	English
Article number	113101
Number of pages	10
Journal	Experimental gerontology
Volume	217
Early online date	19 Mar 2026
DOIs	https://doi.org/10.1016/j.exger.2026.113101
Publication status	Published - May 2026

Bibliographical note

Publisher Copyright:
© 2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

Funding

We gratefully acknowledge the time and dedication of all participants who participated in this study. We thank Research Nurse Alison Campbell (University Hospitals Coventry and Warwickshire NHS Trust) and the nursing team for support in data collection during the whole-room calorimeter study days. The authors are also grateful to Yves Schellenberg from Agropur for providing the Instantized BiPRO whey protein supplement used in this study. This work was conducted while Corbin Griffen was a PhD student at Coventry University and University Hospitals Coventry and Warwickshire NHS Trust. Corbin Griffen is now employed by and affiliated with Decom, Inc., San Diego, California, USA. This publication presents independent research jointly funded by University Hospitals Coventry and Warwickshire NHS Trust & Coventry University and carried out with support of the National Institute of Health Research (NIHR) Coventry and Warwickshire Clinical Research Facility . The views expressed are those of the author(s) and not necessarily those of University Hospitals Coventry and Warwickshire NHS Trust & Coventry University, the NIHR, or the Department of Health.

Funders
University Hospitals Coventry and Warwickshire NHS Trust
National Institute for Health and Care Research
Coventry and Warwickshire Clinical Research Facility
Coventry University

Keywords

Metabolic flexibility
High protein diet
Sarcopenia
Aging
Resistance exercise

Access to Document

10.1016/j.exger.2026.113101Licence: CC BY

Griffen2026VoRFinal published version, 3.04 MBLicence: CC BY

Cite this

@article{f5ab7527f2044548a4874de3f249f6e9,

title = "Metabolic flexibility following resistance exercise and a high protein diet in older men: results from a 12-week randomized controlled trial",

abstract = "Purpose: Aging and sarcopenia are associated with metabolic inflexibility. This study investigated the effects of resistance exercise (RE) and a high protein diet (PRO) on metabolic flexibility (the ability to adjust rates of substrate oxidation to changes in fuel availability) in older men.MethodsIn a pooled groups analysis, 33 healthy older men [(mean±SE) age: 67±1 years; BMI: 25.4±0.4 kg/m2] were randomized to either RE (2×/week; n=17) or no exercise (NE; n=16), and either high protein diet [∼1.6 g/kg/day (∼25\% of energy intake (EI))] via twice daily (25 g) whey protein supplementation (PRO; n=17) or control (CON, 2 × 23.75 g maltodextrin/day; n=16). An exploratory sub-analysis was also conducted between RE+CON (n=8) and RE+PRO (n=9). At baseline and 12 weeks, participants resided in whole-room indirect calorimeters for 24 h for measurement of metabolic flexibility via changes in relative substrate utilization [non-protein respiratory quotient (npRQ)] under different conditions (fasting sleep to awake, step exercise, and 2-h postprandial meal consumption, and peak step exercise to exercise end).ResultsCompared to NE, RE significantly increased (indicating medium-to-large effects on improved metabolic flexibility) ΔnpRQ (awake-sleep) (+0.02±0.004 vs. 0.00±0.05, p=0.01, f=0.48), and ΔnpRQ (steady state exercise-sleep) (p ≤0.045) and ΔnpRQ (peak exercise-exercise end) (p ≤0.04, f=0.39–0.64) for two step exercise bouts performed ∼2 h postprandially. Compared to CON, PRO increased ΔnpRQ (steady state-sleep) for one step exercise bout (+0.02±0.01 vs. -0.002±0.01, p=0.047, f=0.39). No significant differences occurred between the RE+CON and RE+PRO groups (p ≥0.06).ConclusionIn older men, RE improved metabolic flexibility. PRO had a limited benefit. No synergistic effects were observed.",

keywords = "Metabolic flexibility, High protein diet, Sarcopenia, Aging, Resistance exercise",

author = "Corbin Griffen and Derek Renshaw and Michael Duncan and Alexander Dallaway and Hapal Randeva and Weickert, \{Martin O\} and John Hattersley",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = may,

doi = "10.1016/j.exger.2026.113101",

language = "English",

volume = "217",

journal = "Experimental gerontology",

issn = "0531-5565",

publisher = "Elsevier",

}

TY - JOUR

T1 - Metabolic flexibility following resistance exercise and a high protein diet in older men

T2 - results from a 12-week randomized controlled trial

AU - Griffen, Corbin

AU - Renshaw, Derek

AU - Duncan, Michael

AU - Dallaway, Alexander

AU - Randeva, Hapal

AU - Weickert, Martin O

AU - Hattersley, John

PY - 2026/5

Y1 - 2026/5

N2 - Purpose: Aging and sarcopenia are associated with metabolic inflexibility. This study investigated the effects of resistance exercise (RE) and a high protein diet (PRO) on metabolic flexibility (the ability to adjust rates of substrate oxidation to changes in fuel availability) in older men.MethodsIn a pooled groups analysis, 33 healthy older men [(mean±SE) age: 67±1 years; BMI: 25.4±0.4 kg/m2] were randomized to either RE (2×/week; n=17) or no exercise (NE; n=16), and either high protein diet [∼1.6 g/kg/day (∼25% of energy intake (EI))] via twice daily (25 g) whey protein supplementation (PRO; n=17) or control (CON, 2 × 23.75 g maltodextrin/day; n=16). An exploratory sub-analysis was also conducted between RE+CON (n=8) and RE+PRO (n=9). At baseline and 12 weeks, participants resided in whole-room indirect calorimeters for 24 h for measurement of metabolic flexibility via changes in relative substrate utilization [non-protein respiratory quotient (npRQ)] under different conditions (fasting sleep to awake, step exercise, and 2-h postprandial meal consumption, and peak step exercise to exercise end).ResultsCompared to NE, RE significantly increased (indicating medium-to-large effects on improved metabolic flexibility) ΔnpRQ (awake-sleep) (+0.02±0.004 vs. 0.00±0.05, p=0.01, f=0.48), and ΔnpRQ (steady state exercise-sleep) (p ≤0.045) and ΔnpRQ (peak exercise-exercise end) (p ≤0.04, f=0.39–0.64) for two step exercise bouts performed ∼2 h postprandially. Compared to CON, PRO increased ΔnpRQ (steady state-sleep) for one step exercise bout (+0.02±0.01 vs. -0.002±0.01, p=0.047, f=0.39). No significant differences occurred between the RE+CON and RE+PRO groups (p ≥0.06).ConclusionIn older men, RE improved metabolic flexibility. PRO had a limited benefit. No synergistic effects were observed.

AB - Purpose: Aging and sarcopenia are associated with metabolic inflexibility. This study investigated the effects of resistance exercise (RE) and a high protein diet (PRO) on metabolic flexibility (the ability to adjust rates of substrate oxidation to changes in fuel availability) in older men.MethodsIn a pooled groups analysis, 33 healthy older men [(mean±SE) age: 67±1 years; BMI: 25.4±0.4 kg/m2] were randomized to either RE (2×/week; n=17) or no exercise (NE; n=16), and either high protein diet [∼1.6 g/kg/day (∼25% of energy intake (EI))] via twice daily (25 g) whey protein supplementation (PRO; n=17) or control (CON, 2 × 23.75 g maltodextrin/day; n=16). An exploratory sub-analysis was also conducted between RE+CON (n=8) and RE+PRO (n=9). At baseline and 12 weeks, participants resided in whole-room indirect calorimeters for 24 h for measurement of metabolic flexibility via changes in relative substrate utilization [non-protein respiratory quotient (npRQ)] under different conditions (fasting sleep to awake, step exercise, and 2-h postprandial meal consumption, and peak step exercise to exercise end).ResultsCompared to NE, RE significantly increased (indicating medium-to-large effects on improved metabolic flexibility) ΔnpRQ (awake-sleep) (+0.02±0.004 vs. 0.00±0.05, p=0.01, f=0.48), and ΔnpRQ (steady state exercise-sleep) (p ≤0.045) and ΔnpRQ (peak exercise-exercise end) (p ≤0.04, f=0.39–0.64) for two step exercise bouts performed ∼2 h postprandially. Compared to CON, PRO increased ΔnpRQ (steady state-sleep) for one step exercise bout (+0.02±0.01 vs. -0.002±0.01, p=0.047, f=0.39). No significant differences occurred between the RE+CON and RE+PRO groups (p ≥0.06).ConclusionIn older men, RE improved metabolic flexibility. PRO had a limited benefit. No synergistic effects were observed.

KW - Metabolic flexibility

KW - High protein diet

KW - Sarcopenia

KW - Aging

KW - Resistance exercise

UR - https://www.scopus.com/pages/publications/105034690005

U2 - 10.1016/j.exger.2026.113101

DO - 10.1016/j.exger.2026.113101

M3 - Article

C2 - 41864373

SN - 0531-5565

VL - 217

JO - Experimental gerontology

JF - Experimental gerontology

M1 - 113101

ER -

Metabolic flexibility following resistance exercise and a high protein diet in older men: results from a 12-week randomized controlled trial

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this