Ursolic Acid-Standardized Apple Pomace Supplementation for Muscle Strength and Physical Performance in Older Adults With Mild Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Trial

Effects of Ursolic Acid-Standardized Apple Pomace Extract Formulated With Phospholipids on Muscle Strength and Physical Performance in Older Adults With Mild Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

Sarcopenia is an age-related condition characterized by loss of muscle strength and physical performance, leading to increased risk of falls and disability. This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of ursolic acid-standardized apple pomace supplementation on muscle strength and physical performance in older adults with mild sarcopenia. Participants will be randomly assigned to receive either 200 mg/day, 400 mg/day of the supplement, or placebo for 12 weeks. The primary outcome is change in handgrip strength, with additional assessments of physical performance, body composition, fatigue, and quality of life. The study will also evaluate the safety and tolerability of the intervention.

Sarcopenia is an age-related skeletal muscle disorder characterized by progressive decline in muscle strength and physical performance, resulting in increased risk of falls, disability, and loss of independence. Despite its clinical relevance, no pharmacological therapies are currently approved, and management relies primarily on exercise and nutritional strategies, which may be insufficient or impractical for many individuals.

Ursolic acid is a naturally occurring triterpenoid found in apple peel and other plant sources, with preclinical evidence demonstrating beneficial effects on skeletal muscle mass, strength, and metabolic function. These effects have been linked to modulation of anabolic signaling pathways, including insulin and insulin-like growth factor-1 pathways, as well as suppression of muscle atrophy-related genes. Human studies remain limited, particularly in older adults with sarcopenia.

This study is a randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the effects of ursolic acid-standardized apple pomace extract formulated with phospholipids on muscle strength and physical performance in older adults with mild sarcopenia. A total of 105 participants will be randomized in a 1:1:1 ratio to receive either 200 mg/day, 400 mg/day of the active supplement, or placebo for 12 weeks.

The primary endpoint is change in handgrip strength from baseline to Week 6 and Week 12. Key secondary endpoints include measures of lower-limb functional strength and physical performance, including five-times chair stand test, Short Physical Performance Battery score, gait speed, and Timed Up and Go test. Additional outcomes include body composition assessed by bioelectrical impedance analysis, patient-reported outcomes such as fatigue and health-related quality of life, and safety assessments including adverse events and laboratory parameters.

The study is conducted in accordance with Good Clinical Practice and the Declaration of Helsinki, and aims to provide clinical evidence on the efficacy and safety of ursolic acid supplementation in a population with clinically relevant muscle function impairment.

Inclusion Criteria:

• Age 65 to 80 years (inclusive)
• Male or female
• Community-dwelling outpatients
• Able and willing to provide written informed consent
• Able to comply with study procedures and attend scheduled visits
• Able to walk independently (assistive devices permitted) and safely perform physical performance assessments
• Stable medical condition and stable medication regimen for at least 4 weeks prior to screening
• Mild sarcopenia defined as:
• SARC-F score ≥4 or clinical suspicion of sarcopenia, and

Low muscle strength defined as:

Handgrip strength <27 kg for men or <16 kg for women, or Five-times chair stand test >15 seconds or inability to complete without use of arms

- Eligible for body composition assessment using bioelectrical impedance analysis (BIA)

Exclusion Criteria:

• Severe sarcopenia or severe functional impairment precluding safe participation
• Unstable or uncontrolled medical conditions that may interfere with participation or safety
• Severe renal or hepatic disease, including:
• eGFR <30 mL/min/1.73 m²
• Significant liver disease or markedly abnormal liver function tests
• Uncontrolled endocrine or metabolic disorders
• Active malignancy or ongoing cancer treatment
• Use of medications affecting muscle mass or function, including:
• Chronic systemic corticosteroids
• Anabolic steroids or testosterone therapy
• Other investigational muscle-modifying agents
• Recent structured resistance training within the past 3 months
• Use of muscle-targeted supplements (e.g., creatine, HMB) within the previous 4-8 weeks
• Contraindications to BIA (e.g., pacemaker or implanted electronic device)
• Acute illness within 4 weeks prior to screening
• Cognitive impairment preventing informed consent or protocol compliance
• Known allergy or intolerance to ursolic acid or study product components
• Any condition that, in the opinion of the investigator, may compromise safety, compliance, or data integrity