Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial

Francisco M Martínez-Arnau, Rosa Fonfría-Vivas, Cristina Buigues, Yolanda Castillo, Pilar Molina, Aldert J Hoogland, Femke van Doesburg, Leo Pruimboom, Julio Fernández-Garrido, Omar Cauli, Francisco M Martínez-Arnau, Rosa Fonfría-Vivas, Cristina Buigues, Yolanda Castillo, Pilar Molina, Aldert J Hoogland, Femke van Doesburg, Leo Pruimboom, Julio Fernández-Garrido, Omar Cauli

Abstract

Treating sarcopenia in older individuals remains a challenge, and nutritional interventions present promising approaches in individuals that perform limited physical exercise. We assessed the efficacy of leucine administration to evaluate whether the regular intake of this essential amino acid can improve muscle mass, muscle strength and functional performance and respiratory muscle function in institutionalized older individuals. The study was a placebo-controlled, randomized, double-blind design in fifty participants aged 65 and over (ClinicalTrials.gov identifier NCT03831399). The participants were randomized to a parallel group intervention of 13 weeks' duration with a daily intake of leucine (6 g/day) or placebo (lactose, 6 g/day). The primary outcome was to study the effect on sarcopenia and respiratory muscle function. The secondary outcomes were changes in the geriatric evaluation scales, such as cognitive function, functional impairment and nutritional assessments. We also evaluated whether leucine administration alters blood analytical parameters and inflammatory markers. Administration of leucine was well-tolerated and significantly improves some criteria of sarcopenia in elderly individuals such as functional performance measured by walking time (p = 0.011), and improved lean mass index. For respiratory muscle function, the leucine-treated group improved significantly (p = 0.026) in maximum static expiratory force compared to the placebo. No significant effects on functional impairment, cognitive function or nutritional assessment, inflammatory cytokines IL-6, TNF-alpha were observed after leucine administration compared to the placebo. The use of l-leucine supplementation can have some beneficial effects on sarcopenia and could be considered for the treatment of sarcopenia in older individuals.

Keywords: elderly; muscle mass; muscle strength; nutrition; respiratory muscles; sarcopenia.

Conflict of interest statement

Aldert J. Hoogland and Femke van Doesburg are product developers for the company (Bonusan) that provided the leucine and the placebo for the study, and they performed the blind randomization. Aldert J. Hoogland and Femke van Doesburg never saw any of the participants or saw any of the results in this study. The remaining authors (including the corresponding author, Dr. Omar Cauli) declare that they have no competing interests, and they were blind to the drug treatment until the completion of the study.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Effect of Leucine administration on sarcopenia criteria (A) and muscle respiratory sarcopenia (B). (A) Comparison of percentage changes compared to baseline values after leucine or placebo treatment for muscle mass index, handgrip strength and walking time * p = 0.011. (B) Comparison of percentage changes compared to baseline values after leucine or placebo treatment for respiratory muscle function * p = 0.026. Leucine group (LG); placebo group (PG); maximum static inspiratory (MIP) and expiratory (MEP) respiratory pressures at the mouth; peak expiratory flow (PEF).

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