Background and Rationale Physical inactivity is associated with approximately 10% of premature deaths and an estimated €100 billion in annual healthcare costs. Current guidelines recommend at least 150 minutes of moderate-intensity aerobic activity per week alongside resistance training for optimal health. However, when the balance between training load and recovery is disturbed, athletes may develop non-functional overreaching (NFOR), a state of maladaptation characterized by adverse physiological, psychological, and functional outcomes requiring days to weeks for full resolution.
Astragali radix (Astragalus membranaceus), belonging to the Fabaceae family and officially included in the European Pharmacopoeia (8th ed.), is a traditional Chinese herbal medicine known for its antioxidant, anti-inflammatory, and immunomodulatory properties. Prior research has suggested potential benefits in reducing post-exercise inflammatory markers and improving aerobic performance, but its effects during prolonged, structured resistance training programs had not been systematically investigated.
Study Design This was a randomized, double-blind, placebo-controlled trial with 1:1 allocation. Twenty-four moderately active healthy young adults (mean age \~25 years; 13 males/11 females across groups) were enrolled after initial screening of 72 volunteers. Participants were randomly allocated to the ASTRA group (n=13) or PLA group (n=11). Randomization was performed using a computer-generated sequence.
Interventions Participants in the ASTRA group received 480 mg/day of Astragali radix hydroalcoholic extract (Axtragyl®, Giellepi S.p.A., Seregno, Italy; 2 capsules × 240 mg/day) for 10 weeks. The PLA group received matched capsules containing inert substances (microcrystalline cellulose, maltodextrin, magnesium salts of fatty acids) for the same period. Supplement compliance was monitored via daily text messages and collection of returned empty containers.
Training Protocol All participants performed a combined training intervention consisting of: (1) 8 weeks of regular resistance training (RT) at 3 sessions/week, with progressive overload targeting lower limb muscles (back squat, leg press, single-leg extension, single-leg curl, calf raises) at 70-80% of 1RM; followed by (2) 2 weeks of intensified training (IT) at 6 sessions/week, performing 10 sets of 1 repetition at 100% 1RM of leg press and leg extension. All sessions were supervised by experienced personnel.
Assessments
Testing was performed at three time points: baseline (BAS, one week before intervention), after 8 weeks of RT (48 hours post-last session), and after IT completion (24 hours post-last session). Assessments included:
Maximal voluntary isometric torque (MVIT) of knee extensors measured on a custom-built ergometer (primary outcome)
1RM of leg press and leg extension Knee range of motion (ROM) assessed by gyroscope-based goniometry during passive movement Muscle soreness via 100-mm visual analogue scale (VAS) Blood biomarkers: serum CPK, LDH, myoglobin, CRP, IL-6, TNF-α, IGF-1, cortisol, and testosterone (venous blood drawn at BAS, RT, and IT under standardized fasting conditions) Statistical Analysis A general linear model for repeated measures was used, with time (BAS, RT, IT) as within-subject factor and supplementation group (ASTRA vs. PLA) as between-subject factor. Post-hoc comparisons used Bonferroni correction. Effect sizes were reported as partial eta squared (η²). Statistical significance was set at p \< 0.05.
