Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial.
Combining resistance exercise with essential amino acid intake may enhance muscle mass and fitness in older women more effectively than either intervention alone.
Where it sits
this study against the rest of the follistatin-344 corpusSummary and findings
This study measured the effects of combined resistance exercise and essential amino acid intake on muscle fitness and myokine levels in 96 healthy women aged ≥ 65 years over 12 weeks. The RE + EAA group showed significant increases in muscle mass and improvements in fitness tests compared to control and other groups. Notable changes included reductions in myostatin levels and increases in the follistatin/myostatin ratio.
Abstract
<h4>Background</h4>Age-associated sarcopenia and declining physical function in older women are connected to changes in hormones, inflammation, and disrupted protein metabolism. Myokines and cytokines play central roles in muscle atrophy. While both resistance exercise (RE) and essential amino acid (EAA) supplementation are promising interventions, limited randomized trials have assessed their combined effect in healthy elderly populations. Early targeted strategies may help delay sarcopenia and promote healthier aging.<h4>Methods</h4>A 12-week randomized controlled trial was performed involving 96 healthy women aged ≥ 65 years without insulin resistance. Participants were randomized into four groups: control, RE, EAA, or RE + EAA. The intervention consisted of a circuit-based training program conducted three times per week, with each session lasting 60 minutes at moderate intensity. Participants in EAA and RE + EAA groups consumed 5.5g of EAA twice daily. Assessments before and after the intervention included body composition, muscle fitness, serum myokines, and inflammatory cytokines. Data analysis involved two-way repeated measures ANOVA, Bonferroni post-hoc comparisons, and one-way ANOVA for changes in the follistatin/myostatin ratio.<h4>Results</h4>The RE + EAA group demonstrated a significant increase in muscle mass (F(3, 72) = 5.042, <i>p</i> < 0.001, partial η² = 0.174) and greater improvements in the senior fitness test (<i>p</i> ranging from < 0.05 to < 0.001). There was a reduction in myostatin levels (<i>p</i> < 0.05) and an elevation in follistatin in both the RE (<i>p</i> < 0.05) and RE + EAA (<i>p</i> < 0.001) groups. The follistatin/myostatin ratio increased most in the RE + EAA group (F(3, 72) = 5.556, <i>p</i> = 0.002, partial η² = 0.188), with significance versus control (<i>p</i> < 0.001), EAA (<i>p</i> < 0.05) groups. IL-6 and IL-1β were significantly reduced in the RE (<i>p</i> < 0.05) and RE + EAA (<i>p</i> < 0.05) groups, whereas TNF-<i>α</i> decreased only in the RE + EAA group (<i>p</i> < 0.05).<h4>Conclusion</h4>A 12-week intervention combining resistance exercise and essential amino acid supplementation was superior to either intervention alone in enhancing muscle mass, muscle fitness, myokine profiles, and reducing inflammatory markers among healthy older women. These results support the development of early combined interventions for the prevention of sarcopenia and may guide personalized exercise-nutrition prescriptions for optimal aging.<h4>Trial registration</h4>KCT 0010756 (Retrospectively registered; July 15, 2025).
Background
This paper addresses the impact of age-associated sarcopenia and declining physical function in older women, which are linked to hormonal changes and disrupted protein metabolism. Previous research has indicated that myokines and cytokines are crucial in muscle atrophy. While resistance exercise and essential amino acid supplementation have shown promise individually, their combined effects in healthy elderly populations have not been extensively studied. This trial aims to fill that gap and explore potential strategies for delaying sarcopenia.
Methods
The study was a 12-week randomized controlled trial involving 96 healthy women aged ≥ 65 years without insulin resistance. Participants were divided into four groups: control, resistance exercise (RE), essential amino acids (EAA), or RE + EAA. The intervention included a circuit-based training program conducted three times per week, lasting 60 minutes per session at moderate intensity. EAA and RE + EAA groups consumed 5.5g of EAA twice daily, with assessments of body composition, muscle fitness, serum myokines, and inflammatory cytokines before and after the intervention.
Results
The primary endpoint showed a significant increase in muscle mass in the RE + EAA group, with F(3, 72) = 5.042, p < 0.001, and a partial η² of 0.174. Improvements in the senior fitness test were statistically significant with p values ranging from < 0.05 to < 0.001. Myostatin levels were reduced with p < 0.05 in the RE group, while follistatin levels increased significantly in both the RE (p < 0.05) and RE + EAA (p < 0.001) groups. The follistatin/myostatin ratio increased in the RE + EAA group with F(3, 72) = 5.556, p = 0.002, and partial η² = 0.188, showing significance versus control (p < 0.001) and EAA (p < 0.05) groups.
Interpretation
These results suggest that combining resistance exercise with essential amino acid supplementation may provide a more effective intervention for enhancing muscle mass and fitness in older women compared to either intervention alone. However, while the statistical significance is clear, the clinical significance of the effect sizes, particularly for muscle mass increase, should be carefully considered. Limitations such as the small sample size and the retrospective nature of the trial may confound the conclusions drawn from this study.
Key findings
- F(3, 72) = 5.042, p < 0.001, partial η² = 0.174 for muscle mass increase in RE + EAA group.
- p ranging from < 0.05 to < 0.001 for improvements in senior fitness test.
- Reduction in myostatin levels with p < 0.05 in RE group.
- Elevation in follistatin with p < 0.05 in RE group and p < 0.001 in RE + EAA group.
- F(3, 72) = 5.556, p = 0.002, partial η² = 0.188 for follistatin/myostatin ratio increase in RE + EAA group.
- IL-6 and IL-1β were significantly reduced with p < 0.05 in RE and RE + EAA groups.
Limitations
- small sample size n=96
- 12-week follow-up may be too short to assess long-term effects
- retrospectively registered trial raises potential bias concerns