The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis
Open accessAbstract
In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95 % CI 0·50, 1·67; P < 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95 % CI − 0·18, 0·54; P = 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95 % CI − 0·32, 0·44; P = 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.
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A meta-analysis of RCTs revealed a significant increase in the rate of muscle protein fractional synthesis with leucine supplementation in older adults.
“A meta-analysis of RCTs revealed a significant increase in the rate of muscle protein fractional synthesis with leucine supplementation in older adults.47”
From Nutritional and exercise interventions in individuals with sarcopenic obesity around retirement age: a systematic review and meta-analysis (2023) · cites this paper as [47]
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BackgroundEffects of enriched branched-chain amino acid supplementation on sarcopenia
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“Other studies [34, 35] have also reported that leucine supplements helped slow agerelated muscle mass reductions in the elderly.”
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“For example, a systematic review and meta-analysis have indicated that leucine supplementation, a branch-chain amino acid, can enhance muscle protein synthesis in older individuals and counteract age-related declines in muscle mass [17].”
BackgroundBo, T., & Fujii, J. (2024) · Molecules · doi:10.3390/molecules30010056 · Cited by 65 · see citing works
“BCAAs are decreased in the sarcopenic population [144,145], and while the supplementation of BCAAs likely alleviates this symptom, other studies have reported opposite results [146–149].”
The role and therapeutic potential of stem cells in skeletal muscle in sarcopenia
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Sarcopenia: Molecular regulatory network for loss of muscle mass and function
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“When mixtures containing essential, semi-essential and branched chain amino acids are used, blood plasma amino acid levels increase (especially Leu), while 3-methylhistidine and cortisol are decreased [43].”
BackgroundInfluentiall-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function
Sawicka, A., Hartmane, D., Lipinska, P., Wojtowicz, E., Lysiak-Szydlowska, W., & Olek, R. (2018) · Nutrients · doi:10.3390/nu10020255 · Cited by 49 · see citing works
“Therefore, it cannot be ruled out that other supplements affect sarcopenia by their own properties; creatine delays muscle atrophy and improves strength in aging [55], L-leucine increases the muscle protein fractional synthesis rate in the elderly individuals [56], and vitamin D improves muscle strength in people ≥ 65…”
BackgroundGuo, Y., Fu, X., Hu, Q., Chen, L., & Zuo, H. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.929891 · Cited by 44 · see citing works
Skeletal muscle dysfunction with advancing age
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“It is one of these EAA, leucine, that is recognised as the most potent dietary stimulator of MPS [208,209] via stimulation of the mTOR signalling cascade [202], and as such is often suggested as a key nutritional strategy to maintain muscle mass in advancing age.”
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“The impact of dietary protein on frailty is believed to be mainly related to the action of branched chain amino acids (BCAAs) on skeletal muscle [29].”
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“confirmed the efficacy of leucine on muscle protein synthesis, lean body mass and leg lean mass in older people [23].”
BackgroundPreclinical insights into the gut‐skeletal muscle axis in chronic gastrointestinal diseases
Ehlers, L., Bannert, K., Rohde, S., Berlin, P., Reiner, J., Wiese, M. L., Doller, J., Lerch, M. M., Aghdassi, A. A., Meyer, F., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15554 · Cited by 31 · see citing works
Determination of the safety of leucine supplementation in healthy elderly men
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Metabolomics in aging research: aging markers from organs
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Muscle endocrinology and its relation with nutrition
Romagnoli, C., Pampaloni, B., & Brandi, M. L. (2019) · Aging Clinical and Experimental Research · doi:10.1007/s40520-019-01188-5 · Cited by 30 · see citing works
Protein and amino acids for skeletal muscle health in aging
Thalacker‐Mercer, A. E., Riddle, E. S., & Barré, L. K. (2020) · Advances in food and nutrition research · doi:10.1016/bs.afnr.2019.08.002 · Cited by 26 · see citing works
Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions
Warner, E. R., & Satapathy, S. K. (2022) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2022.06.005 · Cited by 26 · see citing works
Navigating the Intersection: Sarcopenia and Sarcopenic Obesity in Inflammatory Bowel Disease
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Kang, M., Kang, M., Yoo, J., Lee, J., Lee, S., Yun, B., Song, M., Kim, J., Kim, H., Yang, J., et al. (2024) · Food & Function · doi:10.1039/d3fo05420a · Cited by 24 · see citing works
Nutrition in Physical Therapist Practice: Setting the Stage for Taking Action
Berner, P., Bezner, J. R., Morris, D. M., & Lein, D. H. (2021) · Physical Therapy · doi:10.1093/ptj/pzab062 · Cited by 24 · see citing works
Pikosky, M. A., Cifelli, C. J., Agarwal, S., & Fulgoni, V. L. I. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.873512 · Cited by 24 · see citing works
Abiri, B., Hosseinpanah, F., Seifi, Z., Amini, S., & Valizadeh, M. (2023) · The journal of nutrition health & aging · doi:10.1007/s12603-023-1986-x · Cited by 27 · see citing works
“In another meta-analysis (40) by the same research group, a low effect (0.18; -0.18 to 0.54 kg) of leucine supplementation on LBM in people aged approximately 65 years and older was observed.”
MethodInfluentialProtein and Peptides for Elderly Health
Shang, N., Chalamaiah, M., Bandara, N., & Wu, J. (2018) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.03.003 · Cited by 24 · see citing works
Safety and Tolerability of Leucine Supplementation in Elderly Men
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Molecular mechanisms and potential interventions during aging-associated sarcopenia
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Leucine and Glutamic Acid as a Biomarker of Sarcopenic Risk in Japanese People with Type 2 Diabetes
Nakajima, H., Okada, H., Kobayashi, A., Takahashi, F., Okamura, T., Hashimoto, Y., Nakanishi, N., Senmaru, T., Ushigome, E., Hamaguchi, M., et al. (2023) · Nutrients · doi:10.3390/nu15102400 · Cited by 21 · see citing works
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“In fact, a meta-analysis demonstrated that leucine supplementation significantly increased myofibrillar protein synthesis compared when with placebo [16,17].”
BackgroundThe nutritional support to prevent sarcopenia in the elderly
Giacosa, A., Barrile, G. C., Mansueto, F., & Rondanelli, M. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1379814 · Cited by 20 · see citing works
Houchins, J. A., Cifelli, C. J., Demmer, E., & Fulgoni, V. L. I. (2016) · The journal of nutrition health & aging · doi:10.1007/s12603-016-0819-6 · Cited by 20 · see citing works
“It is hypothesized that stimulation of muscle protein synthesis at each meal may be beneficial for maintenance of muscle mass (48), however, more data are needed to demonstrate improved lean body mass due to increased muscle protein synthesis in older males and females (49, 50).”
A role for nutritional intervention in addressing the aging neuromuscular junction.
Kougias, D., Das, T., Perez, A., & Pereira, S. (2018) · Nutrition Research · doi:10.1016/j.nutres.2018.02.006 · Cited by 19 · see citing works
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“A separate meta-analysis by Xu et al. [36], which focused specifically on leucine supplementation, analyzed data from 16 randomized controlled trials involving 999 older adults.”
Fu, Z., Wang, Y., Zhao, L., Li, Y., & Song, Q. (2025) · Aging Clinical and Experimental Research · doi:10.1007/s40520-024-02920-6 · Cited by 18 · see citing works
Jin, S. W., Lee, G. H., Kim, J. Y., Kim, C. Y., Choo, Y. M., Cho, W., Han, E. H., Hwang, Y. P., Kim, Y.-A., & Jeong, H. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031229 · Cited by 18 · see citing works
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“higher leucine content) for older people (Katsanos et al. 2006; Xu et al. 2015; Murphy et al. 2016; Phillips 2016).”
BackgroundChae, M., Park, H. S., & Park, K. (2021) · Nutrition Research and Practice · doi:10.4162/nrp.2021.15.2.203 · Cited by 16 · see citing works
“BCAA and leucine have also been reported to increase adenosine triphosphate (ATP) production in the mitochondria [34], thereby promoting muscle protein synthesis [9].”
BackgroundCornelissen, V., Hanssen, H., Hurst, C., Knaier, R., Marqués‐Sulé, E., Moholdt, T. T., Neunhäeuserer, D., Norman, K., Pedretti, R. F. E., Salzwedel, A., et al. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf432 · Cited by 14 · see citing works
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Genton, L., Teta, D., Pruijm, M. T., Stoermann, C., Marangon, N., Mareschal, J., Bassi, I., Wurzner‐Ghajarzadeh, A., Lazarević, V., Cynober, L., et al. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12780 · Cited by 14 · see citing works
Mocini, E., Piciocchi, C., Defeudis, G., & Migliaccio, S. (2025) · Gerontology · doi:10.1159/000546501 · Cited by 13 · see citing works
“Moreover, targeted supplementation might be particularly beneficial for individuals who are unable to consume adequate protein through diet alone [24].”
Zhang, Y., Rao, S., Zhang, X., Peng, Z., Song, W., Xie, S., Cao, H., Zhang, Z., & Yang, W. (2024) · Nutrition Research · doi:10.1016/j.nutres.2024.06.009 · Cited by 12 · see citing works
Leucine Intake and Risk of Impaired Physical Function and Frailty in Older Adults
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Protein: what’s on in research on clinical nutrition
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Mai, K., Cando, P., & Trasino, S. E. (2021) · Journal of Medicinal Food · doi:10.1089/jmf.2021.0094 · Cited by 8 · see citing works
“6 A body of evidence suggests that the proteogenic amino acid leucine can strongly stimulate muscle protein synthesis (MPS) in older adult, 7–10 and thus is now considered a key amino acid in the medical management of sarcopenia.”
Rozga, M., Jones, K., Robinson, J., & Yahiro, A. M. (2021) · Public Health Nutrition · doi:10.1017/s1368980021002184 · Cited by 8 · see citing works
Enhancement of amino acid contents by germination in a Korean weedy rice germplasm
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“[6] Aquatic exercise, [7] various forms of physiotherapy, [8,9] diet change for weight loss, [10,11] glucosamine, and chondroitin sulfate [12,13] are frequently prescribed by primary physicians.”
BackgroundEglseer, D., Traxler, M., & Bauer, S. (2022) · Nutrients · doi:10.3390/nu14214684 · Cited by 7 · see citing works
“They additionally have a high leucine content which is known to increase muscle protein synthesis [23,24].”
BackgroundChang, L. I. U., Huang, J., Hu, Y., & Wu, X. (2022) · Food Science and Technology · doi:10.1590/fst.84722 · Cited by 6 · see citing works
Jin, S. W., Lee, G. H., Kim, J. Y., Kim, C. Y., Choo, Y. M., Cho, W., Choi, J. H., Han, E. H., Hwang, Y. P., & Jeong, H. G. (2021) · Applied Sciences · doi:10.3390/app12010017 · Cited by 5 · see citing works
Bollinger, L. M., Campbell, M. S., & Brault, J. J. (2017) · Nutrition · doi:10.1016/j.nut.2017.07.017 · Cited by 5 · see citing works
Ely, I. A., Paul, M., Wall, J. J. S., Cox, J., Larsen, M. S., Scaife, P. J., Lund, J. N., Breen, L., Wilkinson, D. J., Smith, K., et al. (2025) · Nutrients · doi:10.3390/nu17213410 · Cited by 4 · see citing works
“Despite this, peak plasma LEU concentrations and postprandial rates of MPS have been correlated in cohorts of young [30,31] and older men [32,33], which to our knowledge, is undetermined in women.”
The hallmarks of protein and amino acid restriction in aging and longevity
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“229,230 Leucine supplementation decreases body fat in aging rats, 231 consistent with our finding that leucine restriction in mice increases body weight, adiposity, and fat mass. 34 However, some groups have reported the opposite, finding that leucine restriction is effective at reducing fat mass…”
Potential Benefits of Medical Nutrition Therapy for Timely Ventilator Weaning in the Critically Ill
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The efficacy of nutritional support and its role in the treatment of persons with sarcopenia
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“The exhaustive mention of all the randomized controlled studies dealing with leucine supplementation in the elderly in different experimental contexts is outside the scope of this review, and readers are referred to excellent reviews on that topic [74–79].”
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“In vulnerable populations such as older adults with sarcopenia, it has been suggested that increasing leucine intake may compensate for the blunted muscle PS to anabolic signals and the age-related decline in muscle mass [91 ].”
Andrade, M. F., de Castro, G. S., Gomes, S. P., de Carvalho, M., de Resende, J. C. F., Pires, I. S. O., Faiad, J. Z., Barrére, A. P. N., Venturini, A. L. C., de Souza, R. M., et al. (2026) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2026.103100 · Cited by 2 · see citing works
- Authors
- Xu, Z.-R., Tan, Z.-J., Zhang, Q., Gui, Q.-F., & Yang, Y.-M.
- Affiliations
- First Affiliated Hospital Zhejiang University (CN)
- ORCID
- Zhang, Qin
- Venue
- British Journal of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2014-09-19
- Volume
- 113
- Issue
- 1
- Pages
- 25-34
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2161210071
- Cited by
- 136
- References
- 52
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 9 · 2023: 12 · 2022: 17 · 2021: 12 · 2020: 14 · 2019: 8 · 2018: 15 · 2017: 5 · 2016: 6 · 2015: 2
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Program of Zhejiang Province
- 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, muscle protein synthesis, fractional synthesis rate, lean body mass, leg lean mass, sarcopenia, older adults, age-related muscle loss, muscle protein metabolism
- MeSH terms
- Aged, Body Composition, Humans, Leg, Leucine, Muscle Proteins, Body Mass Index, Randomized Controlled Trials as Topic, Databases, Factual, Muscle, Skeletal, Dietary Supplements
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