Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study

Murphy, Caoileann H; Saddler, Nelson I; Devries, Michaela C; McGlory, Chris; Baker, Steven K; Phillips, Stuart M

doi:10.3945/ajcn.116.136424

Cited by 134Muscle metabolism and nutritionNutrition and Health in AgingMuscle Physiology and Disorders

Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study

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Murphy, Caoileann H, Saddler, Nelson I, Devries, Michaela C, McGlory, Chris, Baker, Steven K, Phillips, Stuart M·2016·The American Journal of Clinical Nutrition

DOI 10.3945/ajcn.116.136424

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Abstract

Background Leucine co-ingestion with lower-protein (LP)-containing meals may overcome the blunted muscle protein synthetic response to food intake in the elderly but may be effective only in individuals who consume LP diets.Objective We examined the impact of leucine co-ingestion with mixed macronutrient meals on integrated 3-d rates of myofibrillar protein synthesis (MyoPS) in free-living older men who consumed higher protein (HP) (1.2 g · kg-1 · d-1) or LP (0.8 g · kg-1 · d-1) in rested and resistance exercise (REX) conditions.Design In a crossover design, 20 healthy older men [aged 65-85 y] were randomly assigned to receive LP or HP diets while ingesting a placebo (days 0-2) and Leu supplement (5 g leucine/meal; days 3-5) with their 3 main daily meals. A bout of unilateral REX was performed during the placebo and Leu treatments. Ingested 2 H 2 O and skeletal muscle biopsies were used to measure the 3-d integrated rate of MyoPS during the placebo and Leu treatments in the rested and REX legs.Results Leucinemia was higher with Leu treatment than with placebo treatment (P < 0.001). MyoPS was similar in LP and HP during both treatments (P = 0.39) but was higher with Leu treatment than with placebo treatment in the rested (pooled mean ± SD: Leu, 1.57% ± 0.11%/d; placebo, 1.48% ± 0.08%/d; main effect of treatment: P < 0.001) and REX (pooled mean: Leu, 1.87% ± 0.09%/d; placebo, 1.71 ± 0.10%/d; main effect of treatment: P < 0.001) legs.Conclusions Leu co-ingestion with daily meals enhances integrated MyoPS in free-living older men in rested and REX conditions and is equally effective in older men who consume daily protein intakes greater than or equal to the RDA. This trial was registered at clinicaltrials.gov as NCT02371278.

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Protein sources high in essential amino acids and leucine are known to raise muscle protein synthesis and might help prevent muscle mass and strength loss during inactivity.
“Supplementing the diet with protein sources rich in EAA and leucine is known to enhance rates of MPS (12,13), and may serve to offset losses in muscle mass and strength during periods of physical inactivity (14).”
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 [12]
Leucine supplementation enhances myofibrillar protein synthesis in older men consuming lower- and higher-protein diets with and without exercise.
“Leucine supplementation enhances myofibrillar protein synthesis in older men consuming lower-and higher-protein diets with and without exercise [84].”
From Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review (2019) · cites this paper as [84]
Acute metabolic and free-living studies provide a rationale for amino acid/protein supplementation to support MPS in older adults.
“Acute metabolic65 and free-living66 studies provide a rationale for amino acid/protein supplementation to support MPS in older adults.”
From Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications (2019) · cites this paper as [66]

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Nabuco, H. C. G., Tomeleri, C. M., Sugihara, P., Fernandes, R. R., Cavalcante, E. F., Antunes, M., Ribeiro, A. S., Teixeira, D. D. C., Silva, A. M., Sardinha, L. B., et al. (2018) · Nutrients · doi:10.3390/nu10050563 · Cited by 88 · see citing works
Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates
Kilroe, S. P., Fulford, J., Holwerda, A. M., Jackman, S. R., Lee, B. P., Gijsen, A. P., van Loon, L. J. C., & Wall, B. T. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00360.2019 · Cited by 85 · see citing works
Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review
Bauer, J. M., Cruz-Jentoft, A. J., Fielding, R. A., Kanis, J. A., Reginster, J.-Y., Bruyère, O., Cesari, M., Chapurlat, R., Al-Daghri, N., Dennison, E., et al. (2019) · Calcified Tissue International · doi:10.1007/s00223-019-00561-w · Cited by 83 · see citing works
Dietary leucine requirement of older men and women is higher than current recommendations
Szwiega, S., Pencharz, P. B., Rafii, M., Lebarron, M., Chang, J. J., Ball, R. O., Kong, D., Xu, L., Elango, R., & Courtney‐Martin, G. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa323 · Cited by 82 · see citing works
Effect of a leucine-rich supplement in combination with nutrition and physical exercise in advanced cancer patients: A randomized controlled intervention trial
Storck, L. J., Ruehlin, M., Gaeumann, S., Gisi, D., Schmocker, M., Meffert, P. J., Imoberdorf, R., Pless, M., & Ballmer, P. E. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.04.008 · Cited by 80 · see citing works
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
Oikawa, S. Y., McGlory, C., D'Souza, L. K., Morgan, A. K., Saddler, N. I., Baker, S. K., Parise, G., & Phillips, S. M. (2018) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy193 · Cited by 76 · see citing works
Self-citation
Protein Supplementation after Exercise and before Sleep Does Not Further Augment Muscle Mass and Strength Gains during Resistance Exercise Training in Active Older Men.
Holwerda, A., Overkamp, M., Paulussen, K., Smeets, J., van Kranenburg, J. V., Backx, E. M. P., Gijsen, A., Goessens, J., Verdijk, L., & van Loon, L. V. (2018) · Journal of NutriLife · doi:10.1093/jn/nxy169 · Cited by 61 · see citing works
Effects of enriched branched-chain amino acid supplementation on sarcopenia
Ko, C.-H., Wu, S., Wang, S., Chang, Y., Chang, C., Kuan, T., Chuang, H.-Y., Chang, C., Chou, W., & Wu, C. (2020) · Aging · doi:10.18632/aging.103576 · Cited by 66 · see citing works
Fish oil-derived n-3 polyunsaturated fatty acids for the prevention and treatment of sarcopenia
Gray, S. R., & Mittendorfer, B. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000441 · Cited by 67 · see citing works
Optimizing Adult Protein Intake During Catabolic Health Conditions
Phillips, S. M., Paddon-Jones, D., & Layman, D. K. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa047 · Cited by 65 · see citing works
Self-citation
A focus on leucine in the nutritional regulation of human skeletal muscle metabolism in ageing, exercise and unloading states
Ely, I. A., Phillips, B. E., Smith, K., Wilkinson, D. J., Piasecki, M., Breen, L., Larsen, M. S., & Atherton, P. J. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.08.010 · Cited by 64 · see citing works
Nutritional Strategies to Offset Disuse-Induced Skeletal Muscle Atrophy and Anabolic Resistance in Older Adults: From Whole-Foods to Isolated Ingredients
Marshall, R. N., Smeuninx, B., Morgan, P. T., & Breen, L. (2020) · Nutrients · doi:10.3390/nu12051533 · Cited by 63 · see citing works
Essential Amino Acid Supplementation Mitigates Muscle Atrophy After Total Knee Arthroplasty
Dreyer, H. C., Owen, E. C., Strycker, L. A., Smolkowski, K., Muyskens, J. B., Kirkpatrick, T. K., Christie, A. D., Kuehl, K. S., Lantz, B. A., Shah, S. N., et al. (2018) · JBJS Open Access · doi:10.2106/jbjs.oa.18.00006 · Cited by 61 · see citing works
Nutrient-rich, high-quality, protein-containing dairy foods in combination with exercise in aging persons to mitigate sarcopenia
Phillips, S. M., & Martinson, W. (2018) · Nutrition reviews · doi:10.1093/nutrit/nuy062 · Cited by 64 · see citing works
Self-citation
A mycoprotein-based high-protein vegan diet supports equivalent daily myofibrillar protein synthesis rates compared with an isonitrogenous omnivorous diet in older adults: a randomised controlled trial
Monteyne, A. J., Dunlop, M. V., Machin, D. J., Coelho, M. D. F. R., Pavis, G. F., Porter, C. C., Murton, A. J., Abdelrahman, D. R., Dirks, M. L., Stephens, F. B., et al. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520004481 · Cited by 59 · see citing works
Daily resistance-type exercise stimulates muscle protein synthesis in vivo in young men.
Holwerda, A., Paulussen, K., Overkamp, M., Smeets, J., Gijsen, A., Goessens, J., Verdijk, L., & van Loon, L. V. (2018) · Journal of applied physiology · doi:10.1152/japplphysiol.00610.2017 · Cited by 51 · see citing works
Where to Find Leucine in Food and How to Feed Elderly With Sarcopenia in Order to Counteract Loss of Muscle Mass: Practical Advice
Rondanelli, M., Nichetti, M., Peroni, G., Faliva, M. A., Naso, M., Gasparri, C., Perna, S., Oberto, L., Paolo, E. D., Riva, A., et al. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2020.622391 · Cited by 55 · see citing works
Interventional strategies to combat muscle disuse atrophy in humans: focus on neuromuscular electrical stimulation and dietary protein
Dirks, M. L., Wall, B. T., & van Loon, L. J. C. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00985.2016 · Cited by 53 · see citing works
Leucine-Enriched Essential Amino Acids Improve Recovery from Post-Exercise Muscle Damage Independent of Increases in Integrated Myofibrillar Protein Synthesis in Young Men
Waskiw‐Ford, M., Hannaian, S. J., Duncan, J., Kato, H., Sawan, S. A., Locke, M., Kumbhare, D. A., & Moore, D. R. (2020) · Nutrients · doi:10.3390/nu12041061 · Cited by 51 · see citing works
Integrated metabolomics and transcriptomics reveal metabolites difference between wild and cultivated Ophiocordyceps sinensis
Zhang, J., Wang, N., Chen, W., Zhang, W., Zhang, H., Yu, H., & Yi, Y. (2022) · Food Research International · doi:10.1016/j.foodres.2022.112275 · Cited by 50 · see citing works
Utilization of Hydroxyl-Methyl Butyrate, Leucine, Glutamine and Arginine Supplementation in Nutritional Management of Sarcopenia—Implications and Clinical Considerations for Type 2 Diabetes Mellitus Risk Modulation
Maykish, A., & Sikalidis, A. K. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10010019 · Cited by 50 · see citing works
The effects of whey, pea, and collagen protein supplementation beyond the recommended dietary allowance on integrated myofibrillar protein synthetic rates in older males: a randomized controlled trial
McKendry, J., Lowisz, C. V., Nanthakumar, A., Macdonald, M. L., Lim, C., Currier, B. S., & Phillips, S. M. (2024) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2024.05.009 · Cited by 53 · see citing works
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Dietary proteins and amino acids in the control of the muscle mass during immobilization and aging: role of the MPS response
Cholewa, J. M., Dardevet, D. P., Lima‐Soares, F., Pessôa, K. D. A., Oliveira, P. H., Pinho, J. R. D. S., Nicastro, H., Xia, Z., Cabido, C. E. T., & Zanchi, N. E. (2017) · Amino Acids · doi:10.1007/s00726-017-2390-9 · Cited by 48 · see citing works
Understanding Muscle Protein Dynamics: Technical Considerations for Advancing Sarcopenia Research
Kim, I., Park, S., Jang, J., & Wolfe, R. R. (2020) · Annals of Geriatric Medicine and Research · doi:10.4235/agmr.20.0041 · Cited by 49 · see citing works
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
Murphy, C. H., Flanagan, E. M., VITO, G. D., Susta, D., Mitchelson, K. A. J., Castro, E. D. M., Senden, J. M., Goessens, J. P. B., Mikłosz, A., Chabowski, A., et al. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa449 · Cited by 47 · see citing works
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Comparative Efficacy of Different Protein Supplements on Muscle Mass, Strength, and Physical Indices of Sarcopenia among Community-Dwelling, Hospitalized or Institutionalized Older Adults Undergoing Resistance Training: A Network Meta-Analysis of Randomized Controlled Trials
Liao, C.-D., Huang, S.-W., Chen, H.-C., Huang, M.-H., Liou, T.-H., & Lin, C.-L. (2024) · Nutrients · doi:10.3390/nu16070941 · Cited by 45 · see citing works
Branched-Chain Amino Acids (Leucine, Isoleucine, and Valine) and Skeletal Muscle
Gorissen, S. H. M., & Phillips, S. M. (2019) · Nutrition and Skeletal Muscle · doi:10.1016/b978-0-12-810422-4.00016-6 · Cited by 45 · see citing works
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The role of protein hydrolysates for exercise-induced skeletal muscle recovery and adaptation: a current perspective
Morgan, P. T., & Breen, L. (2021) · Nutrition & Metabolism · doi:10.1186/s12986-021-00574-z · Cited by 44 · see citing works
Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis
Okekunle, A. P., Zhang, M., Wang, Z., Onwuka, J. U., Wu, X., Feng, R., & Li, C. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1243-7 · Cited by 44 · see citing works
A Novel Amino Acid Composition Ameliorates Short-Term Muscle Disuse Atrophy in Healthy Young Men
Holloway, T. M., McGlory, C., McKellar, S. R., Morgan, A. K., Hamill, M., Afeyan, R., Comb, W. C., Confer, S., Zhao, P., Hinton, M., et al. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00105 · Cited by 43 · see citing works
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Effect of Protein Supplementation During Diet‐Induced Weight Loss on Muscle Mass and Strength: A Randomized Controlled Study
Smith, G. I., Commean, P. K., Reeds, D. N., Klein, S., & Mittendorfer, B. (2018) · Obesity · doi:10.1002/oby.22169 · Cited by 42 · see citing works
Leucine-Enriched Protein Supplementation Increases Lean Body Mass in Healthy Korean Adults Aged 50 Years and Older: A Randomized, Double-Blind, Placebo-Controlled Trial
Kang, Y., Kim, N. H., Choi, Y. J., Lee, Y., Yun, J., Park, S. J., Park, H. S., Chung, Y., & Park, Y. K. (2020) · Nutrients · doi:10.3390/nu12061816 · Cited by 40 · see citing works
Leucine Supplementation in Cancer Cachexia: Mechanisms and a Review of the Pre-Clinical Literature
Beaudry, A. G., & Law, M. L. (2022) · Nutrients · doi:10.3390/nu14142824 · Cited by 40 · see citing works
Dietary protein considerations for muscle protein synthesis and muscle mass preservation in older adults
Olaniyan, E., O'Halloran, F., & McCarthy, A. (2020) · Nutrition research reviews · doi:10.1017/s0954422420000219 · Cited by 31 · see citing works
High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males
Edwards, S. J., Smeuninx, B., McKendry, J., Nishimura, Y., Luo, D., Marshall, R. N., Perkins, M., Ramsay, J., Joanisse, S., Philp, A., et al. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa229 · Cited by 38 · see citing works
Is β-hydroxy β-methylbutyrate an effective anabolic agent to improve outcome in older diseased populations?
ENGELEN, M. P. K. J., & Deutz, N. E. P. (2018) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000459 · Cited by 37 · see citing works
Leucine coingestion augments the muscle protein synthetic response to the ingestion of 15 g of protein following resistance exercise in older men
Holwerda, A. M., Paulussen, K. J. M., Overkamp, M., Goessens, J. P. B., Kramer, I.-F., Wodzig, W. K. W. H., Verdijk, L. B., de Groot, L. C. P. G. M., & van Loon, L. J. C. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00073.2019 · Cited by 36 · see citing works
Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies
Joanisse, S., McKendry, J., Lim, C., Nunes, E. A., Stokes, T., Mcleod, J. C., & Phillips, S. M. (2021) · Clinical Nutrition Open Science · doi:10.1016/j.nutos.2021.01.005 · Cited by 39 · see citing works
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Free Amino Acid Content in Human Milk Is Associated with Infant Gender and Weight Gain during the First Four Months of Lactation
Baldeon, M. E., Zertuche, F., Flores, N., & Fornasini, M. (2019) · Nutrients · doi:10.3390/nu11092239 · Cited by 34 · see citing works
Dietary Protein and Muscle in Aging People: The Potential Role of the Gut Microbiome
Ni Lochlainn, M., Bowyer, R. C. E., & Steves, C. J. (2018) · doi:10.20944/preprints201806.0152.v1 · Cited by 138 · see citing works
Higher Protein Intake Does Not Improve Lean Mass Gain When Compared with RDA Recommendation in Postmenopausal Women Following Resistance Exercise Protocol: A Randomized Clinical Trial
Rossato, L. T., Nahas, P. C., de Branco, F. M. S., Martins, F. M., Souza, A. D. P., Carneiro, M. A. S., Orsatti, F. L., & de Oliveira, E. P. (2017) · Nutrients · doi:10.3390/nu9091007 · Cited by 34 · see citing works
Recent developments in deuterium oxide tracer approaches to measure rates of substrate turnover
Brook, M. S., Wilkinson, D. J., Atherton, P. J., & Smith, K. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000392 · Cited by 27 · see citing works
Effectiveness and cost-effectiveness of personalised dietary advice aiming at increasing protein intake on physical functioning in community-dwelling older adults with lower habitual protein intake: rationale and design of the PROMISS randomised controlled trial
Reinders, I., Wijnhoven, H. A. H., Jyväkorpi, S. K., Suominen, M. H., Niskanen, R. T., Bosmans, J. E., Brouwer, I. A., Fluitman, K. S., Klein, M. C. A., Kuijper, L. D. J., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-040637 · Cited by 24 · see citing works
Leucine Supplementation Has No Further Effect on Training-induced Muscle Adaptations
de Andrade, I. T., Gualano, B., Hevia-Larraín, V., NEVES-JUNIOR, J., Cajueiro, M. O. B., Jardim, F. G. D. A., Gomes, R. L., Artioli, G. G., Phillips, S. M., de Campos‐Ferraz, P. L., et al. (2020) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002307 · Cited by 22 · see citing works
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Novel essential amino acid supplements enriched with L-leucine facilitate increased protein and energy intakes in older women: a randomised controlled trial
Ispoglou, T., Deighton, K., King, R. F., White, H., & Lees, M. (2017) · Nutrition Journal · doi:10.1186/s12937-017-0298-6 · Cited by 21 · see citing works
Association between dietary intake of branched-chain amino acids and sarcopenia and its components: a cross-sectional study
Ebrahimi-Mousavi, S., Hashemi, R., Bagheri, A., Heshmat, R., Motlagh, A. D., & Esmaillzadeh, A. (2022) · Scientific Reports · doi:10.1038/s41598-022-07605-6 · Cited by 21 · see citing works
Effects of Branched-Chain Amino Acids on Skeletal Muscle, Glycemic Control, and Neuropsychological Performance in Elderly Persons with Type 2 Diabetes Mellitus: An Exploratory Randomized Controlled Trial
Matsuda, T., Suzuki, H., Sugano, Y., Suzuki, Y., Yamanaka, D., Araki, R., Yahagi, N., Sekiya, M., Kawakami, Y., Osaki, Y., et al. (2022) · Nutrients · doi:10.3390/nu14193917 · Cited by 20 · see citing works
Nutrient-dense protein as a primary dietary strategy in healthy ageing: please sir, may we have more?
Nunes, E. A., Currier, B. S., Lim, C., & Phillips, S. M. (2021) · Proceedings of the Nutrition Society · doi:10.1017/s0029665120007892 · Cited by 19 · see citing works
Self-citation
Reconsidering the pre-eminence of dietary leucine and plasma leucinemia for predicting the stimulation of postprandial muscle protein synthesis rates
Monteyne, A. J., West, S., Stephens, F. B., & Wall, B. T. (2024) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2024.04.032 · Cited by 20 · see citing works
A potential strategy for counteracting age-related sarcopenia: preliminary evidence of combined exercise training and leucine supplementation
Xia, Z., Cholewa, J. M., Zhao, Y., Yang, Y., Shang, H., Jiang, H., Su, Q., & Zanchi, N. E. (2017) · Food & Function · doi:10.1039/c7fo01181d · Cited by 19 · see citing works
Optimal Protein Intake during Weight Loss Interventions in Older Adults with Obesity
Al-Nimr, R. I. (2019) · Journal of Nutrition in Gerontology and Geriatrics · doi:10.1080/21551197.2018.1544533 · Cited by 18 · see citing works
Peripheral Amino Acid Appearance Is Lower Following Plant Protein Fibre Products, Compared to Whey Protein and Fibre Ingestion, in Healthy Older Adults despite Optimised Amino Acid Profile
Castro, E. D. M., Valli, G., Buffière, C., Guillet, C., Mullen, B., Pratt, J., Horner, K. M., Gola, S., Bader‐Mittermaier, S., Paganini, M., et al. (2022) · Nutrients · doi:10.3390/nu15010035 · Cited by 17 · see citing works
Nutrition strategies to counteract sarcopenia: a focus on protein, LC n -3 PUFA and precision nutrition
Murphy, C. H., McCarthy, S. N., & Roche, H. M. (2023) · Proceedings of The Nutrition Society · doi:10.1017/s0029665123003555 · Cited by 17 · see citing works
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Nutrient modulation in the management of disease-induced muscle wasting
Brook, M. S., Wilkinson, D. J., & Atherton, P. J. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000413 · Cited by 17 · see citing works
Dietary meat and protection against sarcopenia
Lynch, G. S., & Koopman, R. (2018) · Meat Science · doi:10.1016/j.meatsci.2018.06.023 · Cited by 17 · see citing works
Αcute effects of essential amino acid gel-based and whey protein supplements on appetite and energy intake in older women
Butterworth, M., Lees, M. J., Harlow, P., Hind, K., Duckworth, L. C., & Ispoglou, T. (2019) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2018-0650 · Cited by 17 · see citing works
Integrated Myofibrillar Protein Synthesis in Recovery From Unaccustomed and Accustomed Resistance Exercise With and Without Multi-ingredient Supplementation in Overweight Older Men
Bell, K. E., Brook, M. S., Snijders, T., Kumbhare, D. A., Parise, G., Smith, K., Atherton, P. J., & Phillips, S. M. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00040 · Cited by 16 · see citing works
Self-citation
Tart cherry concentrate does not enhance muscle protein synthesis response to exercise and protein in healthy older men
Jackman, S. R., Brook, M. S., Pulsford, R. M., Cockcroft, E., Campbell, M. I., Rankin, D., Atherton, P. J., Smith, K., & Bowtell, J. L. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.06.007 · Cited by 16 · see citing works
Assessing Muscle Protein Synthesis Rates In Vivo in Humans: The Deuterated Water (2H2O) Method
Holwerda, A. M., Atherton, P. J., Smith, K., Wilkinson, D. J., Phillips, S. M., & van Loon, L. J. C. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.09.012 · Cited by 15 · see citing works
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Nutrition and physical activity countermeasures for sarcopenia: Time to get personal?
Murphy, C. H., & Roche, H. M. (2018) · Nutrition Bulletin · doi:10.1111/nbu.12351 · Cited by 15 · see citing works
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Spatial Learning and Motor Deficits in Vacuolar Protein Sorting-associated Protein 13b (Vps13b) Mutant Mouse
Kim, M. J., Lee, R. U., Oh, J., Choi, J. E., Kim, H., Lee, K., Hwang, S., Lee, J., Lee, J., Kaang, B., et al. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.4.485 · Cited by 14 · see citing works
Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a ‘Combined Oral Stable Isotope Assessment of Muscle (COSIAM)’ approach
Cegielski, J., Wilkinson, D. J., Brook, M. S., Boereboom, C., Phillips, B. E., Gladman, J. R. F., Smith, K., & Atherton, P. J. (2021) · GeroScience · doi:10.1007/s11357-021-00386-2 · Cited by 14 · see citing works
Peri-operative protein or amino acid supplementation for total joint arthroplasty: a systematic review and meta-analysis
Khani, Y., Salmani, A. S., Elahi, M., Vahed, I. E., Rad, E. S., Samani, A. B., Karami, S., Nouroozi, M., & Mehrvar, A. (2025) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-05847-4 · Cited by 13 · see citing works
Aminoacidemia following ingestion of native whey protein, micellar casein, and a whey-casein blend in young men
Traylor, D. A., Gorissen, S. H. M., Hopper, H., Prior, T., McGlory, C., & Phillips, S. M. (2018) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2018-0240 · Cited by 13 · see citing works
Self-citation
Daily Leucine Intake Is Positively Associated with Lower Limb Skeletal Muscle Mass and Strength in the Elderly
Lixandrão, M. E., Longobardi, I., Leitão, A. E., Morais, J. V. M., Swinton, P. A., Aihara, A. Y., Goes, P. K., Ugrinowitsch, C., Candow, D. G., Gualano, B., et al. (2021) · Nutrients · doi:10.3390/nu13103536 · Cited by 13 · see citing works
The Phenylalanine Requirement of Elderly Men and Women Measured by Direct 13C Carbon Oxidation Method Is Similar to That of Young Adults
Martin, K. E., Pencharz, P. B., Rafii, M., Ball, R. O., Szwiega, S., Elango, R., & Courtney‐Martin, G. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz137 · Cited by 14 · see citing works
The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle‐aged women is not caused by leucine alone
van Vliet, S., Smith, G. I., Porter, L. C., Ramaswamy, R. S., Reeds, D. N., Okunade, A. L., Yoshino, J., Klein, S., & Mittendorfer, B. (2018) · The Journal of Physiology · doi:10.1113/jp276504 · Cited by 12 · see citing works
How to Increase Muscle Mass in Critically Ill Patients: Lessons Learned from Athletes and Bodybuilders
Gala, K. S., Desai, V. K., Liu, N., Omer, E. M., & McClave, S. A. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00334-0 · Cited by 12 · see citing works
Leucine Intake and Risk of Impaired Physical Function and Frailty in Older Adults
Vega-Cabello, V., Caballero, F. F., Rodríguez‐Artalejo, F., López‐García, E., & Struijk, E. A. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac191 · Cited by 12 · see citing works
Highlight article: Dietary protein and exercise for preservation of lean mass and perspectives on type 2 diabetes prevention
de Sousa, M. D., Soares, D. B. D. S., Caraça, E. R., & Cardoso, R. (2019) · Experimental biology and medicine · doi:10.1177/1535370219861910 · Cited by 11 · see citing works
Early resistance training‐mediated stimulation of daily muscle protein synthetic responses to higher habitual protein intake in middle‐aged adults
Salvador, A. F., McKenna, C. F., Paulussen, K. J. M., Keeble, A. R., Askow, A. T., Fang, H., Li, Z., ULANOV, A. V., Paluska, S. A., Moore, D. R., et al. (2021) · The Journal of Physiology · doi:10.1113/jp281907 · Cited by 11 · see citing works
Effect of High-Protein Diets on Integrated Myofibrillar Protein Synthesis before Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Pilot Study
Howard, E. E., Margolis, L. M., Fussell, M. A., Rios, C. G., Meisterling, E. M., Lena, C. J., Pasiakos, S. M., & Rodriguez, N. R. (2022) · Nutrients · doi:10.3390/nu14030563 · Cited by 11 · see citing works
Protein from whole-body crayfish homogenate may be a high supplier of leucine or branched-chain amino acids – A call for validation on genus Procambarus sp.
Roy, K., Das, K., Petrášková, E., & Kouba, A. (2023) · Food Chemistry · doi:10.1016/j.foodchem.2023.136728 · Cited by 11 · see citing works
Whey protein supplementation 2 hours after a lower protein breakfast restores plasma essential amino acid availability comparable to a higher protein breakfast in overweight adults
Hudson, J., Paddon‐Jones, D., & Campbell, W. W. (2017) · Nutrition Research · doi:10.1016/j.nutres.2017.09.007 · Cited by 10 · see citing works
Contemporary stable isotope tracer approaches: Insights into skeletal muscle metabolism in health and disease
Brook, M. S., & Wilkinson, D. J. (2020) · Experimental Physiology · doi:10.1113/ep087492 · Cited by 10 · see citing works
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Leucine coingestion augments the muscle protein synthetic response to the ingestion of 15 g of protein following resistance exercise in older men
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Self-citation

Authors: Murphy, C. H., Saddler, N. I., Devries, M. C., McGlory, C., Baker, S. K., & Phillips, S. M.
Affiliations: McMaster University (CA)
Corresponding author: Phillips, Stuart M
ORCID: Murphy, Caoileann H
Devries, Michaela C
McGlory, Chris
Baker, Steven K
Phillips, Stuart M
Venue: The American Journal of Clinical Nutrition
Publisher: Elsevier BV
Published: 2016-12
Volume: 104
Issue: 6
Pages: 1594-1606
ISSN: 0002-9165 (ISSN-L)
DOI: 10.3945/ajcn.116.136424
OpenAlex: W2551962319
Cited by: 133
References: 46
Citations by year: 2026: 7 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 12 · 2021: 14 · 2020: 19 · 2019: 18 · 2018: 24 · 2017: 14
FWCI: 12.83
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2260 d)
Locations: American Journal of Clinical Nutrition (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research (MOP 123296)
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: leucine supplementation, myofibrillar protein synthesis, protein intake, older men, resistance training, skeletal muscle, protein synthesis rate, dietary protein, muscle protein synthesis, aging
MeSH terms: Aged, Aged, 80 and over, Amino Acids, Blood Glucose, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Humans, Insulin, Leucine, Male, Muscle Proteins, Myofibrils, Rest, Protein Biosynthesis, Exercise, Body Mass Index, Single-Blind Method, Treatment Outcome, Muscle, Skeletal, Cross-Over Studies, Diet, Protein-Restricted, Postprandial Period, Dietary Supplements, Resistance Training, Recommended Dietary Allowances

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Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study

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