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Completed

NCT Number: NCT07781410

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

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.

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Key information

Age range

60 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Nanyang Technological University

Singapore

About this study

Participation in this study requires a total of 4 weeks of alternate day fasting (ADF) and 3 laboratory visits (sessions) spread over 5-6 weeks. All sessions are done in a fasted and rested state. Participants will complete 4 weeks of ADF alternating between ad libitum feeding days and fasting days consisting of a small midday meal of up to 600 kcal. Supplements will be provided to participants (3 servings on feeding days and 1 serving on fasting day).

Prior to each session, participants are required to:

  • Abstain from any physical activity except activities of daily living for at least 48 hours.
  • Abstain from alcohol and caffeine for at least 24 hours.
  • Fast (i.e., do not eat or drink except plain water) overnight for 10 hours. In consideration of the fasting, these sessions will take place in the morning. To control for diurnal variation, the sessions will be timed such that the same measurements will be taken at approximately the same time of the day (+/- 1 hour difference).
  • Obtain a full night of sleep the night before.

Session 1

  • Read and sign consent form
  • Pre-screening:
  • Subject screening questionnaire
  • Global Physical Activity Questionnaire
  • Body mass
  • Height
  • Resting blood pressure and heart rate
  • Fasting blood glucose (via finger prick)

Session 2 The 4-week alternate-day fasting programme will start within 14 days from session 1

  • Collection of 4 weeks of supplements
  • Body mass
  • Height
  • Resting blood pressure and heart rate
  • Fasting blood glucose (via finger prick)
  • Waist and hip circumference measurements
  • Body composition using bioelectrical impedance analysis and dual-energy X-ray absorptiometry
  • Handgrip strength test
  • Gait speed test
  • Short physical performance battery
  • Complete questionnaires on food craving, mood, appetite, hunger, satiety, diet satisfaction, and cognitive function
  • Blood sample from forearm (35 ml)

Session 3 28 days (4 weeks) after the start of alternate-day fasting

  • Same as session 2 except collection of supplements (not applicable)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

(all of the criteria):

  • 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

Exclusion criteria

(any of the criteria):

  • 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.

Treatment and study plan

Placebo

Dietary Supplement

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

Protein

Dietary Supplement

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

Leucine

Dietary Supplement

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

Primary outcomes

  1. Body Mass

    Time frame: Start and end of 4-week intervention

  2. Lean Mass

    Time frame: Start and end of 4-week intervention

  3. Appendicular Lean Mass

    Time frame: Start and end of 4-week intervention

    Sum of lean mass in upper and lower limbs

  4. Body mass index

    Time frame: Start and end of 4-week intervention

    body mass in kilograms divided by square of height in metres

  5. Lean mass index

    Time frame: Start and end of 4-week intervention

    lean mass in kilograms divided by square of height in metres

  6. Appendicular lean mass index

    Time frame: Start and end of 4-week intervention

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

  7. Fat mass

    Time frame: Start and end of 4-week intervention

  8. Percentage body fat

    Time frame: Start and end of 4-week intervention

  9. Fat mass index

    Time frame: Start and end of 4-week intervention

    Fat mass in kilograms divided by square of height in metres

  10. Trunk fat

    Time frame: Start and end of 4-week intervention

    Fat mass around the trunk

  11. Appendicular fat mass

    Time frame: Start and end of 4-week intervention

    Sum of fat mass in the upper and lower limbs

  12. Appendicular fat mass index

    Time frame: Start and end of 4-week intervention

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

  13. Resting systolic blood pressure

    Time frame: Start and end of 4-week intervention

  14. Resting diastolic blood pressure

    Time frame: Start and end of 4-week intervention

  15. Fasting blood glucose

    Time frame: Start and end of 4-week intervention

  16. HbA1c

    Time frame: Start and end of 4-week intervention

  17. Insulin

    Time frame: Start and end of 4-week intervention

  18. HOMA-IR

    Time frame: Start and end of 4-week intervention

  19. Total cholesterol

    Time frame: Start and end of 4-week intervention

  20. HDL cholesterol

    Time frame: Start and end of 4-week intervention

  21. LDL cholesterol

    Time frame: Start and end of 4-week intervention

  22. Total cholesterol to HDL cholesterol ration

    Time frame: Start and end of 4-week intervention

  23. Triglycerides

    Time frame: Start and end of 4-week intervention

Secondary outcomes

  1. Android fat

    Time frame: Start and end of 4-week intervention

    fat around stomach

  2. Gynoid fat

    Time frame: Start and end of 4-week intervention

    fat around hips and mid section

  3. Bone mineral content

    Time frame: Start and end of 4-week intervention

  4. bone mineral density

    Time frame: Start and end of 4-week intervention

  5. Waist Circumference

    Time frame: Start and end of 4-week intervention

  6. Hip circumference

    Time frame: Start and end of 4-week intervention

  7. Waist-to-hip ratio

    Time frame: Start and end of 4-week intervention

  8. Fat free mass

    Time frame: Start and end of 4-week intervention

    Fat free mass measured using BIA

  9. Skeletal muscle mass

    Time frame: Start and end of 4-week intervention

    Skeletal muscle mass measured using BIA

  10. Appendicular fat-free mass

    Time frame: Start and end of 4-week intervention

    Sum of fat free mass in upper and lower limbs measured using BIA

  11. Visceral fat area

    Time frame: Start and end of 4-week intervention

    Visceral fat area measured using BIA

  12. Fat-free mass index

    Time frame: Start and end of 4-week intervention

    Fat-free mass in kilograms divided by square of height in metres

  13. Skeletal muscle mass index

    Time frame: Start and end of 4-week intervention

    Skeletal muscle mass in kilograms divided by square of height in metres

  14. Appendicular fat-free mass index

    Time frame: Start and end of 4-week intervention

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

  15. Insulin growth factor-1

    Time frame: Start and end of 4-week intervention

  16. Mood

    Time frame: Start and end of 4-week intervention

    Brunel Mood Scale (BRUMS). BRUMS is the modified and shorter version of the Profile of Mood Stats (POMS). The 24-item BRUMS was used to assess mood responses. It has six subscales (tension, depression, anger, vigour, fatigue, and confusion) of four mood descriptors each, with respondents rating how they feel "right now" on a 5-point Likert-type scale (0 = not at all, 1 = a little, 2 = moderately, 3 = quite a bit; 4 = extremely). During its development, the BRUMS showed robust psychometric properties across samples of adult students, adult athletes, young athletes, and schoolchildren, and has since demonstrated psychometric integrity for use with many other population groups (doi.org/10.3390/su13116116).For each subscale, the raw score are summed and converted to a T-score based on the norms published in the paper (doi.org/10.3390/su13116116). Higher T-score for each subscale reflects higher profile of that subscale (i.e. tension, depression, anger, vigour, fatigue, or confusion).

  17. Food craving - habitual

    Time frame: Start and end of 4-week intervention

    The Food Craving Questionnaire-Trait Reduced (FCQ-T-r) measures the habitual (unspecified time frame) trait craving for food in general. It predicts food cravings in daily life. It represents a stable trait but is also sensitive to changes in eating behaviour. The questionnaire consists of 15 questions, participants are required to rate the frequency of each statement with a 6-likert scale (never or not applicable = 1, to always = 6). By summing up the scores of the scales, higher scores represent higher level of food cravings.

  18. Food craving - specific foods

    Time frame: Start and end of 4-week intervention

    Food Craving Inventory (FCI) measures food craving for specific foods and the versions validated for use in United States and United Kingdom were used. Questionnaire items pertaining to specific local foods were also added for a combined total of 61 food items (i.e. questionnaire items). For each item, participants were asked how often they have experienced a craving for that particular food on a 5-point Likert scale (never = 1, to always/almost every day = 5). The higher the score, the higher the food craving.

  19. Eating Behaviour

    Time frame: Start and end of 4-week intervention

    Three-Factor Eating Questionnaire-R18 - cognitive restraint component (TFEQ-r18 Cog). It has 6 items and each scored 1 to 4 for a total of 24 points. The higher the total score, the more disordered the eating behaviour.

  20. Hunger over past 4 weeks

    Time frame: Start and end of 4-week intervention

    Hunger over past 4 weeks. Visual analogue scale 0 to 100. The higher the number the greater the amount of hunger.

  21. Baseline appetite

    Time frame: Start and end of 4-week intervention upon arrival in the laboratory

    Baseline appetite using visual analogue scale 0 to 100. The higher the score, the higher the baseline appetite

  22. Satiety over past 4 weeks

    Time frame: Start and end of 4-week intervention

    Satiety over past 4 weeks. Visual analogue scale 0 to 100. The higher the number, the greater amount of satiety.

  23. Diet satisfaction over past 4 weeks

    Time frame: Start and end of 4-week intervention

    Diet satisfaction over past 4 weeks. Visual analogue scale 0 to 100. The higher the number the greater the satisfaction.

  24. Implicit satiety goal

    Time frame: Start and end of 4-week intervention

    mplicit satiety goal (unconscious, habitual, or subjective levels of fullness that individuals aim to achieve when eating) using visual analogue scale 0 to 100. The higher the number, the greater implicit satiety goal.

  25. Ideal portion size

    Time frame: Start and end of 4-week intervention

    Ideal portion size (IPS). Participants were presented with a diverse range of 25 foods typically consumed in Singapore. The computerised portion selection tasks presented a series of 50 images of each food that increased in portion size in 20 kcal increments (20-1000 kcal). Participants could increase or decrease the portion size by 20 kcal using the left and right arrow-keys on the keyboard and were encouraged to view the full range of portions before selecting their ideal portion. Foods were presented in a randomised order and an average portion size for each participant was calculated by averaging the selected portion sizes of all 25 foods (α = 0.95). This created an overall index of IPS.

  26. Expected satiety

    Time frame: Start and end of 4-week intervention

    Expected satiety (ES) measured using computerised task. The ES task followed the same format as the IPS task, in other words, 50 images were presented depicting 20 kcal increment changes in portion size. This task sought to measure participants' expectations about how satiating a diverse range of foods were. Larger portions selected indicated that participants require larger quantities of the food to delay the onset of hunger, in other words they have lower expected satiety. The same 25 foods presented in the IPS were also presented in the ES in a randomised order and were averaged to create an overall index of ES (α = 0.95).

  27. Food-related characteristics

    Time frame: Start and end of 4-week intervention

    A single image of each food item was presented to participants alongside questions of food-related characteristics. Participants were asked to rate how filling they expected each food to be (not filling at all (0) to very filling (100)), how much they like each food in general (not at all (0) to very much (100)) and how often they eat each food (never (0) to more than once a week (5)). Each food was presented in a randomised order and average scores across all 25 foods for participants perceptions of how filling, frequently consumed and preference for foods were calculated.

  28. Handgrip strength

    Time frame: Start and end of 4-week intervention

    Measurement of handgrip strength using a handheld dynamometer

  29. Short physical performance battery

    Time frame: Start and end of 4-week intervention

    Standardised physical performance test

  30. 6m gait speed

    Time frame: Start and end of 4-week intervention

    Gait speed over 6m

Other outcomes

  1. Height

    Time frame: Start and end of 4-week intervention

  2. Hydration status

    Time frame: Start and end of 4-week intervention

    Intracellular water (litre)/extracellular water (litre). This ratio is a reflection of the hydration status in the body. Hydration status can affect the body composition measurements using BIA.

  3. SGP/ALT

    Time frame: Start and end of 4-week intervention

    blood biomarker of liver function

  4. SGOT/AST

    Time frame: Start and end of 4-week intervention

    blood biomarker of liver function

  5. Serum sodium

    Time frame: Start and end of 4-week intervention

  6. Serum potassium

    Time frame: Start and end of 4-week intervention

  7. Serum urea

    Time frame: Start and end of 4-week intervention

  8. Serum creatinine

    Time frame: Start and end of 4-week intervention

  9. Full blood count

    Time frame: Start and end of 4-week intervention

  10. Weekly physical activity level

    Time frame: 1-2 weeks before the start of the intervention and for each week of the 4-week intervention

    Participants complete the type, intensity and duration of each physical activity during the week similar to Global Physical Activity Questionnaire (GPAQ) developed by the WHO. Each activity is calculated in Metabolic Equivalent (MET) value. Moderate MET value is 4.0 and vigorous MET value is 8.0 while for transport domains MET value is 4.0.

  11. Food diary

    Time frame: 4-day/week during the 4-week intervention

    Participants have to record their food intake on 4-day/week

  12. Sleep diary

    Time frame: Daily during the 4-week intervention

    Participants have to log their sleep time, wake up time and subjective sleep quality daily

Sponsors and collaborators

Lead sponsor

Nanyang Technological University

Other

Collaborators

  • Ministry of Education, Singapore

Registry information

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Aug 24, 2026
Registry last updated
Aug 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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