Calorie Restriction With Leucine Supplementation

Calorie Restriction With Leucine Supplementation in Postmenopausal Women

The purpose of this study is to determine whether consuming additional leucine during calorie restriction induced weight loss has beneficial or harmful effects on multi-organ (liver, muscle, adipose tissue) insulin sensitivity, colonocyte proliferation rates, the gut microbiome, muscle mass and function, and bone mineral density in obese, postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Obesity; Menopause; Sarcopenia; Osteoporosis
• Intervention / Treatment: Behavioral: Weight loss with normal protein and leucine intake; Behavioral: Weight loss with protein/leucine supplementation

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Obese with body mass index (BMI) between 30 and 40 kg/m2
• Postmenopausal
• Sedentary (i.e., less than 1.5 hours of exercise per week)

Exclusion Criteria:

• Individuals with diabetes and/or uncontrolled hypertension
• Individuals with hepatitis B and/or C
• Individuals who smoke
• Individuals with an allergy to whey protein

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Weight maintenance; Weight maintenance with normal protein and leucine intake
Active Comparator: Weight loss with normal protein intake	Behavioral: Weight loss with normal protein and leucine intake; Goal of 8 to 10% weight loss while consuming the recommended daily allowance of protein (i.e, 0.8 grams of protein per kg body weight per day).
Experimental: Weight loss with leucine supplementation	Behavioral: Weight loss with protein/leucine supplementation; Goal of 8 to 10% weight loss while consuming 150% of the recommended daily allowance of protein (i.e., 1.2 grams of protein per kg body weight per day) with the additional protein given in the form of whey protein, which has a high leucine content.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle mass	We will measure total appendicular skeletal muscle mass by using dual-energy X-ray absorptiometry (DXA) and thigh muscle volume by magnetic resonance imaging (MRI)	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Change in muscle strength	We will evaluate muscle strength by administering maximum one repetition strength and isokinetic strength tests.	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Change in bone mineral density and bone mineral content	We will evaluate total bone mass and total body and regional bone mineral density by using dual X-ray energy absorptiometry (DXA).	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in skeletal muscle insulin sensitivity	We will evaluate insulin sensitivity using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope labeled tracer infusions	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Change in bacterial populations found in the stool		Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Change in cell proliferation (growth) rates in the colon	We will examine colon cell proliferation rates using stable isotope labelled tracer methods in conjunction with sigmoid colon biopsy samples	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Determine the acute effect of leucine ingestion on skeletal muscle insulin sensitivity	We will evaluate insulin sensitivity using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope labeled tracer infusions	Prior to starting the weight loss or maintenance intervention
Determine the acute effect of leucine ingestion on muscle protein metabolism	We will assess rates of muscle protein synthesis, breakdown and net protein balance using stable isotope labeled tracer methods during postabsorptive conditions and during insulin infusion with or without leucine ingestion.	Prior to starting the weight loss or maintenance intervention

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Ajinomoto Co., Inc.

Publications and helpful links

General Publications

• Smith GI, Yoshino J, Stromsdorfer KL, Klein SJ, Magkos F, Reeds DN, Klein S, Mittendorfer B. Protein Ingestion Induces Muscle Insulin Resistance Independent of Leucine-Mediated mTOR Activation. Diabetes. 2015 May;64(5):1555-63. doi: 10.2337/db14-1279. Epub 2014 Dec 4.
• Harris LLS, Smith GI, Patterson BW, Ramaswamy RS, Okunade AL, Kelly SC, Porter LC, Klein S, Yoshino J, Mittendorfer B. Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance. Diabetes. 2017 Jul;66(7):1871-1878. doi: 10.2337/db16-1475. Epub 2017 May 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 20, 2012
• First Posted (Estimate): December 28, 2012

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Bone Diseases; Muscular Atrophy; Atrophy; Bone Diseases, Metabolic; Sarcopenia; Osteoporosis
• Other Study ID Numbers: CRL-201102153