Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial.

BACKGROUND

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.

METHODS

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.

RESULTS

The RE + EAA group demonstrated a significant increase in muscle mass (F(3, 72) = 5.042, p < 0.001, partial η² = 0.174) and greater improvements in the senior fitness test (p ranging from < 0.05 to < 0.001). There was a reduction in myostatin levels (p < 0.05) and an elevation in follistatin in both the RE (p < 0.05) and RE + EAA (p < 0.001) groups. The follistatin/myostatin ratio increased most in the RE + EAA group (F(3, 72) = 5.556, p = 0.002, partial η² = 0.188), with significance versus control (p < 0.001), EAA (p < 0.05) groups. IL-6 and IL-1β were significantly reduced in the RE (p < 0.05) and RE + EAA (p < 0.05) groups, whereas TNF-α decreased only in the RE + EAA group (p < 0.05).

CONCLUSION

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.

TRIAL REGISTRATION

KCT 0010756 (Retrospectively registered; July 15, 2025).