Role of Leucine on Muscle Preservation During Weight Loss in Older Men

NCT07781410 | Completed DMC

• 1 other identifier: IRB-2022-090
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Overweight and obesity are part of a global health epidemic. However, older adults trying to lose weight face a dual challenge: first, muscle mass and strength naturally decline at an accelerating rate with age; second, effective weight loss diets like alternate-day fasting (ADF) are typically accompanied by significant muscle loss. Together, these factors can increase the risk of developing sarcopenia, a muscle disease characterized by critical losses in muscle mass and strength, especially when overweight or obese older adults try to lose weight through dieting alone. While high protein diets have often been advocated as a muscle preserving strategy when losing weight, recently, high leucine intake has been promoted for its critical role in stimulating muscle protein synthesis (MPS) with lower overall protein consumption, potentially reducing calorie intake while maintaining muscle during weight loss. Nonetheless, the effects of body mass-scaled protein and leucine intakes on muscular outcomes during weight loss remain uncertain. This study examines the effects of body mass-scaled protein and leucine supplementation on body composition during four weeks of ADF in older men.

Conditions

Overweight and Obese Adults; BMI>=23 kg/m2

Keywords

Overweight; Obese; Intermittent Fasting; Alternate Day Fasting; Protein; Leucine; Skeletal muscle; muscle; blood health; mood; appetite; food craving

Outcome Measures

Primary Outcomes (23)

• Body Mass

  Start and end of 4-week intervention

• Lean Mass

  Start and end of 4-week intervention

• Appendicular Lean Mass

  Sum of lean mass in upper and lower limbs

  Start and end of 4-week intervention

• Body mass index

  body mass in kilograms divided by square of height in metres

  Start and end of 4-week intervention

• Lean mass index

  lean mass in kilograms divided by square of height in metres

  Start and end of 4-week intervention

• Appendicular lean mass index

  Appendicular lean mass in kilograms divided by square of height in metres

  Start and end of 4-week intervention

• Fat mass

  Start and end of 4-week intervention

• Percentage body fat

  Start and end of 4-week intervention

• Fat mass index

  Fat mass in kilograms divided by square of height in metres

  Start and end of 4-week intervention

• Trunk fat

  Fat mass around the trunk

  Start and end of 4-week intervention

• Appendicular fat mass

  Sum of fat mass in the upper and lower limbs

  Start and end of 4-week intervention

• Appendicular fat mass index

  Appendicular fat mass in kilograms divided by square of height in metres

  Start and end of 4-week intervention

• Resting systolic blood pressure

  Start and end of 4-week intervention

• Resting diastolic blood pressure

  Start and end of 4-week intervention

• Fasting blood glucose

  Start and end of 4-week intervention

• HbA1c

  Start and end of 4-week intervention

• Insulin

  Start and end of 4-week intervention

• HOMA-IR

  Start and end of 4-week intervention

• Total cholesterol

  Start and end of 4-week intervention

• HDL cholesterol

  Start and end of 4-week intervention

• LDL cholesterol

  Start and end of 4-week intervention

• Total cholesterol to HDL cholesterol ration

  Start and end of 4-week intervention

• Triglycerides

  Start and end of 4-week intervention

Secondary Outcomes (30)

• Android fat

  Start and end of 4-week intervention

• Gynoid fat

  Start and end of 4-week intervention

• Bone mineral content

  Start and end of 4-week intervention

• bone mineral density

  Start and end of 4-week intervention

• Waist Circumference

  Start and end of 4-week intervention

Other Outcomes (12)

• Height

  Start and end of 4-week intervention

• Hydration status

  Start and end of 4-week intervention

• SGP/ALT

  Start and end of 4-week intervention

Study Arms (3)

Control

PLACEBO COMPARATOR

0.0 g/kg protein and 0.0 g/kg leucine supplementation per meal

Dietary Supplement: Placebo

Protein

EXPERIMENTAL

0.4 g/kg protein and 0.04 g/kg leucine supplementation per meal

Dietary Supplement: Protein

Leucine

EXPERIMENTAL

0.0 g/kg protein and 0.08 g/kg leucine supplementation per meal

Dietary Supplement: Leucine

Interventions

Placebo DIETARY_SUPPLEMENT

Control (placebo supplements) 0.0 g/kg protein and 0.0 g/kg leucine supplementation per meal

Control

Protein DIETARY_SUPPLEMENT

Protein supplements: 0.4 g/kg protein and 0.04 g/kg leucine supplementation per meal

Protein

Leucine DIETARY_SUPPLEMENT

Leucine supplementation: 0.0 g/kg protein and 0.08 g/kg leucine supplementation per meal

Leucine

Eligibility Criteria

• Age: 60 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Of Asian descent
• Do not smoke or use tobacco products (including shisha)
• Have a body mass index (BMI = body mass in kilograms divided by the square of height in metres) ≥ 23 kg/m2

You may not qualify if:

• Unable to adhere to the requirements regarding physical activity and diet as stated in the research methodologies. All supplements; including but not limited to vitamins, minerals, amino acids and proteins; which are not provided by this research, and traditional Chinese medicine are not allowed.
• Vegetarians or vegans due to potential differences in responses and that the supplements provided may contain dairy products.
• Allergic or intolerant to milk. The supplement that you will be required to consume may contain milk proteins, and lactose (milk sugar).
• Failed an exercise stress test.
• Have any health condition(s) that would be made worse by fasting.
• History of familial leucine-sensitive hypoglycaemia, i.e., highly symptomatic hypoglycaemia triggered by protein meals or the amino acid, leucine.
• Have diabetes, pre-diabetes, or abnormally high fasting blood glucose (\> 6.0 mmol/L).
• Have uncontrolled hypertension (≥ 150/90 mmHg for ≥ 80 years old, ≥ 140/90 mmHg for \< 80 years old).
• Have liver or kidney conditions.
• Have existing musculoskeletal conditions that could be exacerbated by the physical assessments in this study.
• More than twice per week of regular and structured resistance training (lifting weights).
• Competed in resistance exercise-related competitions in the past 6 months.
• Taking long-term prescribed medications (including traditional Chinese medicine and other alternative medicine), drugs, steroids, or hormones that can affect any of the measurements in this study.
• Have electrical implant (such as pacemaker, implantable cardioverter defibrillator or neurostimulator), metal or plastic implant/rod/plate, or joint replacement in the body as these objects can affect the accuracy of the body composition measurement.

Sponsors & Collaborators

• Nanyang Technological University: lead
• Ministry of Education, Singapore: collaborator

Study Sites (1)

Nanyang Technological University

Singapore, Singapore

Location

MeSH Terms

Conditions

Overweight; Obesity; Intermittent Fasting

Interventions

Proteins; Leucine

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fasting; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three-arm, double-blind, randomized controlled trial

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 24, 2026
• Study Start: November 14, 2022
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: August 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

SG (1)