Leucine partially protects muscle mass and function during bed rest in middle-aged adults
Open accessAbstract
Background Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults.Objective The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest.Design We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ∙ kg(-1) ∙ meal(-1)) or an alanine control (CON group) during 14 d of bed rest.Results Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05).Conclusions Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.
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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).”
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“Similarly, protein supplementation in middle-age and older adults during longer periods of bed rest ( i.e ., 10– 14 days) has demonstrated protective effects on lean mass, 11,12 but this strategy was not effective to maintain muscle size of healthy older adults during 5-days of cast immobilization.”
Supplements with purported effects on muscle mass and strength
Valenzuela, P. L., Morales, J. S., Emanuele, E., Pareja-Galeano, H., & Lucia, A. (2019) · European Journal of Nutrition · doi:10.1007/s00394-018-1882-z · Cited by 78 · see citing works
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
“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).”
BackgroundKouw, I. W. K., Groen, B. B. L., Smeets, J. S. J., Kramer, I. F., van Kranenburg, J. M. X., Nilwik, R., Geurts, J. A. P., ten Broeke, R. H. M., Poeze, M., van Loon, L. J. C., et al. (2018) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2018.06.018 · Cited by 75 · see citing works
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Howard, E. E., Pasiakos, S. M., Fussell, M. A., & Rodriguez, N. R. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa015 · Cited by 73 · see citing works
“5 g of leucine to every meal during 7 d of immobilization in young adults also had no effect on preserving muscle mass or function (61), despite the previously reported benefit during 7 d of bed rest (6).”
BackgroundInfluentialSoendenbroe, C., Andersen, J. L., & Mackey, A. L. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00174.2021 · Cited by 65 · see citing works
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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
“Specifically, several bed rest studies in middle-aged and older adults suggest that improving dietary protein quality via supplemental leucine has the potential to positively impact and partially protect muscle lean mass (76, 101).”
BackgroundResultSelf-citationMarshall, R. N., Smeuninx, B., Morgan, P. T., & Breen, L. (2020) · Nutrients · doi:10.3390/nu12051533 · Cited by 63 · see citing works
Fuchs, C. J., Kuipers, R., Rombouts, J., Brouwers, K., Schrauwen-Hinderling, V. B., Wildberger, J., Verdijk, L., & van Loon, L. V. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112159 · Cited by 57 · see citing works
Jiao, J., Han, S.-F., Zhang, W., Xu, J., Tong, X., Yin, X.-B., Yuan, L., & Qin, L. (2016) · Food & Nutrition Research · doi:10.3402/fnr.v60.31304 · Cited by 56 · see citing works
“Even in middle-aged adults during 14 days of bed rest, leucine prevented an increase in body fat percentage (24).”
BackgroundMitchell, C., D'Souza, R., Mitchell, S., Figueiredo, V., Miller, B., Hamilton, K., Peelor, F. F., Coronet, M., Pileggi, C., Durainayagam, B. R., et al. (2018) · Journal of applied physiology · doi:10.1152/japplphysiol.00803.2017 · Cited by 53 · see citing works
“Nutritional interventions therefore may present a practical countermeasure to limit muscle loss during muscular disuse and immobility and further aid recovery (17, 25, 29, 57, 81).”
BackgroundInfluentialDirks, 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
“In the scientific literature, muscle disuse in humans is generally studied using a limb immobilization or bed rest model in healthy volunteers (53, 82, 144, 149, 176).”
BackgroundResultGil, S. D. S., Júnior, G. N. D. O., Sarti, F. M., Filho, W. J., Longobardi, I., Turri, J. A. O., Shinjo, S. K., Ferriolli, E., Avelino‐Silva, T. J., Busse, A. L., et al. (2022) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2022.11.013 · Cited by 53 · see citing works
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
“During bed-rest conditions, a leucine-supplemented diet (0.06 g/kg/meal) has also been shown to protect against muscle loss after 7 days, but not after 14 days in middle-aged subjects (English et al. 2016).”
BackgroundMethodInfluentialBackx, E. M. P., Horstman, A. M. H., Marzuca-Nassr, G. N., van Kranenburg, J. M. X., Smeets, J. S. J., Fuchs, C. J., Janssen, A. A. W., de Groot, C. P. G. M., Snijders, T., Verdijk, L. B., et al. (2018) · Nutrients · doi:10.3390/nu10050635 · Cited by 47 · see citing works
“determined the impact of leucine supplementation during two weeks of bedrest in young individuals [64].”
BackgroundWinnard, A., Scott, J., Waters, N., Vance, M., & Caplan, N. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01046 · Cited by 47 · 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
“06 g/kg/meal) has been shown to have some protective effect during disuse (11) although we acknowledge this is a disparate observation (13) who provided 2.”
BackgroundMiki, A., Hashimoto, Y., Matsumoto, S., Ushigome, E., Fukuda, T., Senmaru, T., Tanaka, M., Yamazaki, M., & Fukui, M. (2017) · Journal of Diabetes Research · doi:10.1155/2017/7985728 · Cited by 41 · see citing works
“Essential amino acids, especially leucine, are potent stimulators of muscle protein synthesis [25, 26], through activation of mammalian target of rapamycin pathway [27].”
BackgroundWang, L., Wu, T., Zhang, Y., Yang, K., He, Y., Deng, K., Liang, C., & Gu, Y. (2022) · International Dairy Journal · doi:10.1016/j.idairyj.2022.105542 · Cited by 41 · see citing works
Kilroe, S. P., Fulford, J., Jackman, S. R., Holwerda, A. M., Gijsen, A. P., van Loon, L. J. C., & Wall, B. T. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa136 · Cited by 39 · see citing works
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PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging
Petrocelli, J. J., & Drummond, M. J. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17228650 · Cited by 39 · see citing works
Potential of Food Protein-Derived Bioactive Peptides against Sarcopenia: A Comprehensive Review
Zhu, X., Wang, J., Lu, Y., Zhao, Y., Zhang, N., Wu, W., Zhang, Y., & Fu, Y. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c09094 · Cited by 38 · see citing works
Protecting Skeletal Muscle with Protein and Amino Acid during Periods of Disuse
Galvan, E., Arentson‐Lantz, E. J., Lamon, S., & Paddon‐Jones, D. (2016) · Nutrients · doi:10.3390/nu8070404 · Cited by 38 · see citing works
“However, during the final days of bed rest, the rate of loss in leucine-supplemented subjects was the same as the control condition [7].”
BackgroundInfluentialSelf-citationBaron, J. E., Parker, E. A., Duchman, K. R., & Westermann, R. W. (2020) · Orthopaedic Journal of Sports Medicine · doi:10.1177/2325967120930296 · Cited by 38 · see citing works
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Immunological Endotyping of Chronic Critical Illness After Severe Sepsis
Fenner, B. P., Darden, D. B., Kelly, L. S., Rincon, J. C., Brakenridge, S. C., Larson, S. D., Moore, F. A., Efron, P. A., & Moldawer, L. L. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2020.616694 · Cited by 38 · see citing works
“Leucine is another amino acid that shows promising results, as it decreases muscle protein catabolism and induces protein synthesis (150).”
BackgroundENGELEN, 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
Petrocelli, J. J., Mahmassani, Z. S., Fix, D. K., Montgomery, J. A., Reidy, P. T., McKenzie, A. I., de Hart, N. M. M. P., Ferrara, P. J., Kelley, J. J., Eshima, H., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202100883r · Cited by 37 · see citing works
Countering disuse atrophy in older adults with low-volume leucine supplementation
Arentson‐Lantz, E. J., Fiebig, K. N., Anderson-Catania, K. J., Deer, R., Wacher, A., Fry, C. S., Lamon, S., & Paddon‐Jones, D. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00847.2019 · Cited by 35 · see citing works
Self-citationArentson-Lantz, E. J., Galvan, E., Ellison, J., Wacher, A., & Paddon-Jones, D. (2019) · The journals of gerontology. Series A, Biological sciences and medical sciences · doi:10.1093/gerona/glz003 · Cited by 35 · see citing works
“For example, supplementation with large quantities of protein or amino acids provides a robust anabolic stimulus and can partially protect muscle mass and function during inactivity (9,12).”
BackgroundMethodResultInfluentialSelf-citationRossato, 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
“Middle-aged adults have similar negative metabolic consequences of aging [5], and postmenopausal women are included in this context.”
BackgroundDeane, C. S., Ely, I. A., Wilkinson, D. J., Smith, K., Phillips, B. E., & Atherton, P. J. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120007879 · Cited by 32 · see citing works
Smeuninx, B., Elhassan, Y., Sapey, E., Rushton, A. B., Morgan, P. T., Korzepa, M., Belfield, A. E., Philp, A., Brook, M. S., Gharahdaghi, N., et al. (2023) · The Journal of Physiology · doi:10.1113/jp285130 · Cited by 31 · see citing works
“The decline in iMyoPS and muscle mass during bed-rest is underlined by diminished aMyoPS rates (Drummond et al., 2012; English et al., 2016).”
Meza-Valderrama, D., Sánchez‐Rodríguez, D., Messaggi-Sartor, M., Muñoz-Redondo, E., Morgado-Pérez, A., Tejero-Sánchez, M., Gil, E. D. J., Bañuelos, N. L., & Marco, E. (2023) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2023.105323 · Cited by 30 · see citing works
α-Lactalbumin: Functional properties and potential health benefits
Ge, X., Zhang, J., Regenstein, J. M., Liu, D., Huang, Y., Qiao, Y., & Zhou, P. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.104371 · Cited by 30 · see citing works
Angiotensin II inhibition: a potential treatment to slow the progression of sarcopenia
Kingsley, J., Torimoto, K., Hashimoto, T., & Eguchi, S. (2021) · Clinical Science · doi:10.1042/cs20210719 · Cited by 26 · see citing works
Leucine Protects Against Skeletal Muscle Atrophy in Lipopolysaccharide-Challenged Rats
Wan, J., Chen, D., Yu, B., Luo, Y., Mao, X., Zheng, P., Yu, J., Luo, J., & He, J. (2016) · Journal of Medicinal Food · doi:10.1089/jmf.2016.3759 · Cited by 26 · see citing works
Exercise Countermeasures to Neuromuscular Deconditioning in Spaceflight
English, K. L., Bloomberg, J. J., Mulavara, A. P., & Ploutz‐Snyder, L. L. (2019) · Comprehensive physiology · doi:10.1002/cphy.c190005 · Cited by 31 · see citing works
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Protein Requirements in Critically Ill Older Adults
Deer, R., & Volpi, E. (2018) · Nutrients · doi:10.3390/nu10030378 · Cited by 25 · see citing works
Effects of high-protein intake on bone turnover in long-term bed rest in women
Heer, M., Baecker, N., Frings-Meuthen, P., Graf, S., Zwart, S. R., Biolo, G., & Smith, S. M. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0292 · Cited by 24 · see citing works
“Given that a positive effect such as maintaining muscle mass by maintaining muscle protein synthesis (English et al. 2016; Moore 2014) would be very beneficial in inactivity such as BR, increased protein intake might still increase bone Page 5 of 40”
BackgroundResultAn overview of nutritional strategies for recovery process in sports-related muscle injuries
Quintero, K. J., Resende, A. D. S., Leite, G. S. F., & Lancha, A. H. (2018) · Nutrire · doi:10.1186/s41110-018-0084-z · Cited by 23 · see citing works
“Furthermore, they summarized that the ingestion of 10 g/day of essential amino acids (EAA) in free form or as part of the meal timing above, this for maximized the stimuli of muscle protein synthesis (MPS), as well is important that adding sources of leucine to a moderate amount of protein consumed during regular meal…”
BackgroundResultTreffel, L., Massabuau, N., Zuj, K. A., Custaud, M., Gauquelin‐Koch, G., Blanc, S., Gharib, C., & Millet, C. (2017) · Pain Research and Management · doi:10.1155/2017/9602131 · Cited by 21 · see citing works
Protein Valuation in Food Choice Is Positively Associated with Lean Mass in Older Adults
Buckley, C. M., Austin, S., Corfe, B. M., Green, M. A., Johnstone, A. M., Stevenson, E., Williams, E. A., & Brunstrom, J. M. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz124 · Cited by 20 · see citing works
“Intervention studies have demonstrated a causal association: muscle function is impaired when protein intake is reduced (8) and protein supplementation produces a corresponding improvement (9).”
Adeva‐Andany, M. M., Fernández‐Fernández, C., López-Pereiro, Y., Calvo‐Castro, I., & Carneiro-Freire, N. (2021) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2021.06.025 · Cited by 19 · see citing works
Baptista, I. L., Silvestre, J. G., Silva, W. J., Labeit, S., & Moriscot, A. S. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2614-z · Cited by 19 · see citing works
Have, G. A. M. T., Jansen, L. T., Schooneman, M. G., ENGELEN, M. P. K. J., & Deutz, N. E. P. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00384.2020 · Cited by 18 · see citing works
Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats
Viana, L. R., Chiocchetti, G. D. M. E., Oroy, L., Vieira, W. F., Busanello, E. N. B., Marques, A. C., Salgado, C. D. M., de Oliveira, A. L. R., Vieira, A. S., Suarez, P. A. S., et al. (2021) · Cells · doi:10.3390/cells10123272 · Cited by 18 · see citing works
“, metabolism, mass, and function, during relatively brief periods of physical inactivity in middle-aged adults [28].”
BackgroundReider, L. M., Owen, E. C., Dreyer, H. C., Fitton, L., & Willey, M. (2023) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00836-0 · Cited by 18 · see citing works
“Protection of muscle mass is associated with retention of strength and endurance [90].”
Daily blood flow restriction does not preserve muscle mass and strength during 2 weeks of bed rest
Fuchs, C. J., Hermans, W. J. H., Nyakayiru, J., Weijzen, M. E. G., Smeets, J. S. J., Aussieker, T., Senden, J. M., Wodzig, W. K. W. H., Snijders, T., Verdijk, L. B., et al. (2024) · The Journal of Physiology · doi:10.1113/jp286065 · Cited by 18 · see citing works
Deer, R., Dickinson, J. M., Fisher, S. R., Ju, H., & Volpi, E. (2016) · Contemporary Clinical Trials · doi:10.1016/j.cct.2016.05.001 · Cited by 18 · see citing works
“Recent data also indicate that the benefits of protein/ amino acid supplementation on skeletal muscle health can be achieved during a 2–3 week time frame in clinical populations[77] or models of clinical settings[49].”
BackgroundMethodArentson‐Lantz, E. J., Ruff, Z. V., Connolly, G., Albano, F. R., Kilroe, S. P., Wacher, A., Campbell, W. W., & Paddon‐Jones, D. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.10.010 · Cited by 17 · see citing works
Self-citationD’Souza, R. F., Zeng, N., Figueiredo, V. C., Markworth, J. F., Durainayagam, B. R., Mitchell, S. M., Fanning, A. C., Poppitt, S. D., Cameron‐Smith, D., & Mitchell, C. J. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201701028 · Cited by 17 · see citing works
Nutritional Support to Counteract Muscle Atrophy
Owens, D. J. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1435-3_22 · Cited by 16 · see citing works
Nygård, L. K., Mundal, I. P., Dahl, L., Benth, J. Š., & Rokstad, A. M. M. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-023845 · Cited by 15 · see citing works
van den Hoek, A. M., Zondag, G. C. M., Verschuren, L., de Ruiter, C., Attema, J., de Wit, E. C., Schwerk, A. M. K., Guigas, B., Lek, S., Rietman, A., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.012 · Cited by 15 · see citing works
Fernandez‐Gonzalo, R., McDonnell, A. C., Simpson, E. J., Macdonald, I. A., Rullman, E., & Mekjavić, I. B. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.676501 · Cited by 14 · see citing works
Yarar‐Fisher, C., Polston, K. F. L., Eraslan, M., Henley, K. Y., Kınıklı, G. İ., Bickel, C. S., Windham, S. T., McLain, A., Oster, R. A., & Bamman, M. M. (2018) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01029.2017 · Cited by 14 · see citing works
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Self-citationVariation in Protein Origin and Utilization: Research and Clinical Application
Paddon‐Jones, D., Coss‐Bu, J. A., Morris, C. R., Phillips, S. M., & Wernerman, J. (2017) · Nutrition in Clinical Practice · doi:10.1177/0884533617691244 · Cited by 14 · see citing works
“The time-sensitive protective effect was facilitated by the partial preservation of muscle protein synthesis and accompanied by the partial conservation of muscular strength, endurance, and aerobic capacity.(41) While data from bedrest and acute research studies are encouraging, leucine supplementation is not uncondit…”
BackgroundSelf-citationSkeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition
Cruz, A., Ferian, A., Alves, P. K. N., Silva, W. J., Bento, M. R., Gasch, A., Labeit, S., & Moriscot, A. S. (2020) · DNA and Cell Biology · doi:10.1089/dna.2020.5423 · Cited by 14 · see citing works
Carbone, J. W., Phillips, S. M., Weaver, C. M., Hughes, J. M., & Pasiakos, S. M. (2024) · Advances in Nutrition · doi:10.1016/j.advnut.2024.100347 · Cited by 15 · see citing works
DeVirgiliis, L., Goode, N. J., McDowell, K. W., English, K. L., Novo, R., Botros, V., Agwu, G., Scott, J. M., & Ploutz‐Snyder, L. L. (2025) · Experimental Physiology · doi:10.1113/ep091595 · Cited by 15 · see citing works
“Specific scenarios in which higher protein intakes have been shown to exert protective effects include periods of negative energy balance (Carbone et al., 2019; Hiroux et al., 2022; Longland et al., 2016; Pasiakos et al., 2013) and during reduced physical activity (English et al., 2016).”
Self-citationMechanotransduction for Muscle Protein Synthesis via Mechanically Activated Ion Channels
Mirzoev, T. M. (2023) · Life · doi:10.3390/life13020341 · Cited by 14 · see citing works
Noone, J., Damiot, A., Kenny, H., Chery, I., Zahariev, A., Normand, S., Crampes, F., de Glisezinski, I., Rochfort, K. D., Laurens, C., et al. (2023) · The Journal of Physiology · doi:10.1113/jp284734 · Cited by 13 · see citing works
“This is concerning because the authors draw conclusions that are reliant on normalization of the data.”
Nutrition for Master Athletes: Is There a Need for Specific Recommendations?
Louis, J. B., Vercruyssen, F., Dupuy, O., & Bernard, T. (2019) · Journal of Aging and Physical Activity · doi:10.1123/japa.2019-0190 · Cited by 14 · see citing works
Metabolic pathways at the crossroads of diabetes and inborn errors
Goetzman, E. S., Gong, Z., Schiff, M., Wang, Y., & Muzumdar, R. H. (2017) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-017-0091-x · Cited by 15 · see citing works
“Dietary BCAA supplementation (leucine in particular) can reduce fat mass, body weight, and even improve glucose metabolism (Arrieta-Cruz et al 2016; Binder et al 2013; English et al 2016; Heimann et al 2016).”
Neuromuscular Electrical Stimulation and Anabolic Signaling in Patients with Stroke
Mettler, J. A., Bennett, S. M., Doucet, B. M. M., & Magee, D. M. (2017) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2017.07.019 · Cited by 12 · see citing works
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“Physical inactivity alone contributes to a host of negative outcomes including impaired insulin action, loss of lean muscle mass, fatigue, impaired functional capacity, and increased morbidity and mortality (English et al., 2016; Arentson-Lantz et al., 2019, 2020; Wang et al., 2020).”
BackgroundSelf-citationAlves, P. K. N., Schauer, A., Augstein, A., Jarabo, M. P., Männel, A., Barthel, P., Vahle, B., Moriscot, A. S., Linke, A. H.-P., & Adams, V. (2024) · Cells · doi:10.3390/cells13060502 · Cited by 12 · see citing works
“Beneficial effects of leucine supplementation on sarcopenia and muscle strength especially in elderly people have been reported (for review see [48,49]), but positive effects were also seen in middle-aged adults during prolonged bed rest [29].”
BackgroundQuantifying Leg Muscle Disuse Atrophy During Bed Rest Using DXA, CT, and MRI
Fuchs, C. J., Hermans, W. J. H., van den Hurk, J., Wiggins, C. J., Widholm, P., Leinhard, O. D., Veeraiah, P., Wildberger, J. E., Prompers, J. J., & van Loon, L. J. C. (2025) · European Journal of Sport Science · doi:10.1002/ejsc.12299 · Cited by 12 · see citing works
“…applied to estimate leg lean mass, serving as a proxy for muscle, and to monitor its changes over time in various settings (Mcglory et al. 2019; Edwards et al. 2020; Brook et al. 2022; Wall et al. 2014; Fuchs et al. 2023; Maden‐Wilkinson et al. 2013; Dirks et al. 2016; English et al. 2016).”
Ye, H., Yang, J., Luo, Y., Long, Y., Zhang, J.-H., Zhong, Y., Gao, F., & Wang, M. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1093988 · Cited by 11 · see citing works
“Of the included 20 RCTs, the dietary supplement was leucine in four studies (20, 32, 35, 36), essential amino acids/carbohydrates in the five (41, 43–46), protein in seven (21, 23, 33, 34, 38, 40, 47),”
BackgroundMethodInfluentialGuo, Y., Wang, H., Tang, Y., Wang, Y., Zhang, M., Yang, Z., Nyirimigabo, E., Wei, B. K., Lu, Z., & Ji, G. (2018) · Protein & Cell · doi:10.1007/s13238-018-0504-0 · Cited by 11 · see citing works
“, 1995), has been regarded as a potential pharmaconutrient for the treatment of numerous muscle wasting conditions (Bauer et al., 2015; Tsien et al., 2015; English et al., 2016).”
BackgroundWhey Protein Nutrition in Sports: Action Mechanisms and Gaps in Research
Pan, D., Zhang, Z., Liu, N., & Ashaolu, T. J. (2025) · Current Nutrition Reports · doi:10.1007/s13668-025-00673-w · Cited by 10 · see citing works
“Older adults experience age-related anabolic resistance that reduces their responsiveness to protein intake [96].”
Moradpour, G., Amini, M., Moeinvaziri, N., Hosseini, S. V., Rajabi, S., Clark, C. C. T., Hosseini, B., Vafa, L., & Haghighat, N. (2021) · Obesity Surgery · doi:10.1007/s11695-021-05761-8 · Cited by 10 · see citing works
Rozhkov, S. V., Sharlo, K. A., Shenkman, B. S., & Mirzoev, T. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052751 · Cited by 9 · see citing works
Hu, M., Li, W., Yin, Q., Liu, Y., Chen, L., Ru, Q., Xu, G., & Wu, Y. (2025) · npj Microgravity · doi:10.1038/s41526-025-00515-7 · Cited by 9 · see citing works
“Bed rest evidence shows leucine and its metabolite HMB partially preserve muscle mass and function in inactive adults 86,87 , with meta-analyzes con fi rming HMB ’ s ef fi cacy against disuse atrophy 88 , while combining higher protein doses with exercise protects muscle in the elderly 89 .”
- Authors
- English, K. L., Mettler, J. A., Ellison, J. B., Mamerow, M. M., Arentson-Lantz, E., Pattarini, J. M., Ploutz-Snyder, R., Sheffield-Moore, M., & Paddon-Jones, D.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Universities Space Research Association (US)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 103
- Issue
- 2
- Pages
- 465-473
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC4733256
- OpenAlex
- W2212801556
- Cited by
- 162
- References
- 64
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 10 · 2023: 16 · 2022: 10 · 2021: 20 · 2020: 27 · 2019: 15 · 2018: 17 · 2017: 22 · 2016: 6
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Texas Space Grant Consortium
- National Space Biomedical Research Institute (R01NR012973, NNJ08ZSA002N, P30 AG024832)
- National Institutes of Health (UL1TR000071, AG024832)
- National Institute on Aging (P30AG024832)
- National Institute of Nursing Research (R01NR012973)
- National Center for Research Resources (UL1RR029876)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007539)
- 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, bed rest, muscle atrophy, skeletal muscle protein synthesis, middle-aged adults, physical inactivity, muscle function, lean mass loss, muscle quality, quadriceps strength, body composition, alanine, mTOR signaling, translation initiation, sarcopenia prevention, endurance performance, body fat percentage
- MeSH terms
- Bed Rest, Biopsy, Needle, Body Composition, Carbon Isotopes, Double-Blind Method, Exercise Test, Female, Humans, Leucine, Male, Middle Aged, Muscle Proteins, Muscular Atrophy, Oxygen Consumption, Signal Transduction, Absorptiometry, Photon, Muscle, Skeletal, Dietary Supplements, Muscle Development, Whole Body Imaging
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