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

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

Status
Completed
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07781410
Enrollment
80
Registered
2026-08-24
Start date
2022-11-14
Completion date
2023-06-20
Last updated
2026-08-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

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

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.

Detailed description

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)

Interventions

DIETARY_SUPPLEMENTPlacebo

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

DIETARY_SUPPLEMENTProtein

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

DIETARY_SUPPLEMENTLeucine

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

Sponsors

Nanyang Technological University
Lead SponsorOTHER
Ministry of Education, Singapore
CollaboratorOTHER_GOV

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Three-arm, double-blind, randomized controlled trial

Eligibility

Sex/Gender
MALE
Age
60 Years to No maximum
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Body MassStart and end of 4-week intervention
Lean MassStart and end of 4-week intervention
Appendicular Lean MassStart and end of 4-week interventionSum of lean mass in upper and lower limbs
Body mass indexStart and end of 4-week interventionbody mass in kilograms divided by square of height in metres
Lean mass indexStart and end of 4-week interventionlean mass in kilograms divided by square of height in metres
Appendicular lean mass indexStart and end of 4-week interventionAppendicular lean mass in kilograms divided by square of height in metres
Fat massStart and end of 4-week intervention
Percentage body fatStart and end of 4-week intervention
Fat mass indexStart and end of 4-week interventionFat mass in kilograms divided by square of height in metres
Trunk fatStart and end of 4-week interventionFat mass around the trunk
Appendicular fat massStart and end of 4-week interventionSum of fat mass in the upper and lower limbs
Appendicular fat mass indexStart and end of 4-week interventionAppendicular fat mass in kilograms divided by square of height in metres
Resting systolic blood pressureStart and end of 4-week intervention
Resting diastolic blood pressureStart and end of 4-week intervention
Fasting blood glucoseStart and end of 4-week intervention
HbA1cStart and end of 4-week intervention
InsulinStart and end of 4-week intervention
HOMA-IRStart and end of 4-week intervention
Total cholesterolStart and end of 4-week intervention
HDL cholesterolStart and end of 4-week intervention
LDL cholesterolStart and end of 4-week intervention
Total cholesterol to HDL cholesterol rationStart and end of 4-week intervention
TriglyceridesStart and end of 4-week intervention

Secondary

MeasureTime frameDescription
Android fatStart and end of 4-week interventionfat around stomach
Gynoid fatStart and end of 4-week interventionfat around hips and mid section
Bone mineral contentStart and end of 4-week intervention
bone mineral densityStart and end of 4-week intervention
Waist CircumferenceStart and end of 4-week intervention
Hip circumferenceStart and end of 4-week intervention
Waist-to-hip ratioStart and end of 4-week intervention
Fat free massStart and end of 4-week interventionFat free mass measured using BIA
Skeletal muscle massStart and end of 4-week interventionSkeletal muscle mass measured using BIA
Appendicular fat-free massStart and end of 4-week interventionSum of fat free mass in upper and lower limbs measured using BIA
Visceral fat areaStart and end of 4-week interventionVisceral fat area measured using BIA
Fat-free mass indexStart and end of 4-week interventionFat-free mass in kilograms divided by square of height in metres
Skeletal muscle mass indexStart and end of 4-week interventionSkeletal muscle mass in kilograms divided by square of height in metres
Appendicular fat-free mass indexStart and end of 4-week interventionAppendicular fat-free mass in kilograms divided by square of height in metres
Insulin growth factor-1Start and end of 4-week intervention
MoodStart and end of 4-week interventionBrunel 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).
Food craving - habitualStart and end of 4-week interventionThe 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.
Food craving - specific foodsStart and end of 4-week interventionFood 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.
Eating BehaviourStart and end of 4-week interventionThree-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.
Hunger over past 4 weeksStart and end of 4-week interventionHunger over past 4 weeks. Visual analogue scale 0 to 100. The higher the number the greater the amount of hunger.
Baseline appetiteStart and end of 4-week intervention upon arrival in the laboratoryBaseline appetite using visual analogue scale 0 to 100. The higher the score, the higher the baseline appetite
Satiety over past 4 weeksStart and end of 4-week interventionSatiety over past 4 weeks. Visual analogue scale 0 to 100. The higher the number, the greater amount of satiety.
Diet satisfaction over past 4 weeksStart and end of 4-week interventionDiet satisfaction over past 4 weeks. Visual analogue scale 0 to 100. The higher the number the greater the satisfaction.
Implicit satiety goalStart and end of 4-week interventionmplicit 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.
Ideal portion sizeStart and end of 4-week interventionIdeal 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.
Expected satietyStart and end of 4-week interventionExpected 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).
Food-related characteristicsStart and end of 4-week interventionA 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.
Handgrip strengthStart and end of 4-week interventionMeasurement of handgrip strength using a handheld dynamometer
Short physical performance batteryStart and end of 4-week interventionStandardised physical performance test
6m gait speedStart and end of 4-week interventionGait speed over 6m

Countries

Singapore

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 25, 2026