Protein2026-06

Short-term isolated leucine supplementation was not associated with improvements in muscle mass or function in patients with head and neck cancer: A randomized, double-blind, proof-of-concept trial with an elderly non-cancer comparator cohort.

Andrade Márcia Fábia, de Castro Gabriela Salim, Gomes Silvio Pires, de Carvalho Marcelo et al. — Clinical nutrition ESPEN

Summary

This study investigated whether taking leucine, an amino acid, could help head and neck cancer patients maintain or gain muscle. It found that while healthy older adults showed a small increase in muscle mass with leucine supplementation, cancer patients did not experience improvements in muscle mass or function. This suggests that leucine alone may not be enough to combat muscle loss in cancer.

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Key points

Leucine, an amino acid, was studied for its potential to help muscle in cancer patients.
Head and neck cancer patients who took leucine did not show improvements in muscle mass or function.
Healthy older adults in the study experienced a modest increase in muscle mass with leucine supplementation.
The findings suggest that leucine alone may not be sufficient to counter muscle loss in cancer.

What the study looked at

What question the study asked: This study investigated whether taking leucine, a specific amino acid known to support muscle protein building, could help head and neck cancer patients improve their muscle mass and physical function. Researchers also compared these effects to those in healthy older adults. How it was studied: Forty-one participants, including 23 head and neck cancer patients and 18 healthy older adults, took part in a randomized, double-blind trial. For four weeks, half of each group received 6 grams of leucine daily, while the other half received a placebo (non-essential amino acids). Researchers measured changes in muscle mass using advanced scans (DXA) and assessed muscle strength, physical performance, and other health markers. What it found: The study found that leucine supplementation did not lead to improvements in muscle mass or function for head and neck cancer patients. In contrast, healthy older adults who took leucine experienced a small, but statistically significant, increase in muscle mass. No significant changes were observed in muscle strength or inflammatory markers in any group.

Dietary takeaway

This study suggests that for head and neck cancer patients, simply adding leucine supplements may not be enough to combat muscle loss. Instead, a comprehensive approach including adequate overall protein intake from diverse food sources, along with physical activity and addressing inflammation, might be more effective. For healthy older adults, ensuring sufficient protein, including leucine-rich foods like meat, dairy, and legumes, could support muscle maintenance, but remember that this is just one study and more research is needed.

Abstract

BACKGROUND & AIMS: Cancer cachexia is a multifactorial syndrome characterized by muscle mass loss, systemic inflammation, and anabolic resistance, negatively impacting patients' quality of life and survival. Leucine, an essential branched-chain amino acid (BCAA), has shown promising effects on protein synthesis, particularly in the elderly, but its effects in cancer patients remain underexplored. This study aimed to evaluate the short-term effects of isolated leucine supplementation on skeletal muscle mass and related outcomes in patients with head and neck cancer (HNC), in an elderly non-cancer cohort as a physiological comparator. METHODS: This randomized, double-blind, proof-of-concept trial was conducted with 41 participants, divided into two groups: 23 cancer patients and 18 non-cancer (NC) patients. Participants received either 6 g/day of isolated leucine or non-essential amino acids (NEAA) comparator for 4 weeks. The primary endpoint was the change in appendicular skeletal muscle mass index (ASMMI) assessed by dual-energy X-ray absorptiometry (DXA). Secondary and exploratory outcomes included skeletal muscle mass index assessed by bioelectrical impedance analysis (BIA), muscle strength, physical performance, phase angle, quality of life, nitrogen balance, and inflammatory markers. The 3-way ANOVA was used to assess pre- and post-supplementation effects. Multiple comparisons were performed using the Bonferroni test. A 2-way ANOVA or the Mann-Whitney test followed by Tukey's multiple comparisons, when appropriate, were applied. Pearson's correlation was used for parametric data, and Spearman's correlation for non-parametric data. RESULTS: Leucine supplementation was associated with a modest increase in ASMMI in the non-cancer leucine group compared with its comparator (Δ 0.31 ± 0.13 vs. 0.08 ± 0.19 kg/m; p = 0.01). No significant between-group differences were observed in HNC patients. In CL group, ASMMI correlated strongly with PA (r = 0.821, p = 0.01) and moderately with CC (r = 0.673, p = 0.02). In CP group, ASMMI correlated with PA (r = 0.734, p = 0.02); in NCP group, SMMI correlated with HGS (r = 0.862, p = 0.01). Secondary outcomes, including muscle strength, gait speed, phase angle, and inflammatory markers, did not differ significantly between groups. Protein intake remained below recommended levels, and nitrogen balance was negative across cohorts. CONCLUSION: In this short-term, proof-of-concept study, isolated leucine supplementation was associated with modest gains in muscle mass in elderly individuals without cancer but was not linked with improvements in muscle mass or function in patients with HNC. These findings suggest that supplementation with isolated leucine supplementation alone is insufficient to counteract cancer-related muscle waste and should be investigated as part of multimodal interventions addressing nutrition, inflammation, and physical activity.

View on PubMed →DOI: 10.1016/j.clnesp.2026.103100