Independent and Combined Effects of Resistance Exercise Training and β-hydroxy β-methylbutyrate Plus Vitamin D

Study Overview
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Brief Summary
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During middle-age, humans begin to lose muscle mass and strength. With increasing age the deterioration of muscle health is associated with a decline in quality of life and the loss of independence. β-hydroxy β-methylbutyrate (HMB) plus Vitamin D (VitD) have been proposed to increase skeletal muscle mass, contractile function and improve body composition but has yet to be evaluated in middle-aged women. The overall goal of this study is to determine the effects of HMB +VitD supplementation during 12 weeks of resistance exercise training or a non-exercise control on body composition, skeletal muscle size, and skeletal muscle function in middle-aged women.

Detailed Description
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To determine if HMB+VitD supplementation is an effective strategy to help prevent the loss of skeletal muscle size, skeletal muscle function and body composition in middle-aged women, forty eight women (45-60 yrs old) will be recruited to complete a 12-week intervention (n=12 per group; 4 groups). Participants will be randomized to complete a non-exercise control period or a resistance exercise training program. In a double-blinded fashion, participants in the non-exercise or resistance exercise groups will be randomized to consume either placebo or HMB+VitD. Before and after each intervention the investigators will evaluate skeletal muscle size, skeletal muscle function, and body composition.

Official Title
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Independent and Combined Effects of Resistance Exercise Training and β-hydroxy β-methylbutyrate Plus Vitamin D on Body Composition and Skeletal Muscle Health

Conditions
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Aging, Skeletal Muscle

Intervention / Treatment
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* Behavioral: Non-Exercise Control
* Behavioral: Resistance Exercise Training
* Dietary Supplement: Placebo
* Dietary Supplement: HMB+VitD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women between 45 and 60 years old Women with a BMI < 35 kg/m2 Sedentary (< 30 minutes of structured physical activity 3 times per week) Weight stable for 3 months prior (+/- 5kg) Exclusion Criteria: Body mass index > 35 kg/m2 Type 1 or Type 2 diabetes Uncontrolled hypertension Active cancer, cancer in remission, or having received treatment for any form of cancer in the previous 5 years Cardiovascular disease (e.g., peripheral artery disease and peripheral vascular disease) Uncontrolled thyroid function Chronic and/or regular consumption of medication known to influence skeletal muscle metabolism Use of Vitamin D (>2000 IU) or β-hydroxy β-methylbutyrate Tobacco use Any condition that limits exercise training (e.g., chronic obstructive pulmonary disease, neuromuscular disorder, moderate or severe cognitive impairment, Alzheimer's disease, vertigo, dizziness) High alcohol consumption defined as more than 8 drinks per week for women Unwilling to undergo any study-related procedures Pregnancy Abnormal liver or kidney enzymes determined in blood chemistry panel Bleeding/clotting disorders or blood thinning medications (e.g., warfarin, heparin)

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to 1 of 4, 12-week interventions. In a double-blinded fashion, participants will be randomized to consume either placebo or HMB + VitD supplementation. Group 1 will serve as a non-exercise control with placebo; Group 2 will serve as a non-exercise control with β-hydroxy β-methylbutyrate + Vitamin D; Group 3 will complete resistance exercise training with placebo; Group 4 will complete resistance exercise training with β-hydroxy β-methylbutyrate + Vitamin D
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Non-exercise control with placebo<br>Participants will be asked to maintain their normal physical activity and dietary habits during the 12-week intervention. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 placebo capsules (calcium lactate), twice a day with a meal or snack for a total of 6 capsules per day. Placebo capsules match the size, color, weight, and number of capsules per dose compared to the β-hydroxy β-methylbutyrate (HMB) Plus Vitamin D (VitD) capsules. | Behavioral: Non-Exercise Control<br>* Participants will not perform structured exercise and will continue with their normal physical activity for 12-weeks.<br>Dietary Supplement: Placebo<br>* Participants will be given placebo capsules to consume for 12-weeks.<br>|
| Experimental: Non-exercise control with HMB+VitD<br>Participants will be asked to maintain their normal physical activity and dietary habits during the 12-week intervention. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 HMB+VitD capsules, twice a day with a meal or snack for a total of 6 capsules per day. Each capsule contains 500 mg calcium HMB and 333.33 IU Vitamin D for a total of 3.0 g HMB and 2000 IU Vitamin D per day. | Behavioral: Non-Exercise Control<br>* Participants will not perform structured exercise and will continue with their normal physical activity for 12-weeks.<br>Dietary Supplement: HMB+VitD<br>* Participants will be given HMB+VitD capsules to consume for 12-weeks<br>|
| Active Comparator: Resistance exercise training with placebo<br>Participants will complete 12-weeks (3 days per week) of a whole-body progressive resistance exercise training program. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 placebo capsules (calcium lactate), twice a day with a meal or snack for a total of 6 capsules per day. Participants will be asked to take capsules  30-60 minutes before resistance exercise. Placebo capsules match the size, color, weight, and number of capsules per dose compared to the HMB + VitD capsules. | Behavioral: Resistance Exercise Training<br>* Participants will complete a 12-week whole-body progressive resistance exercise training program.<br>Dietary Supplement: Placebo<br>* Participants will be given placebo capsules to consume for 12-weeks.<br>|
| Experimental: Resistance exercise training with HMB+VitD<br>Participants will complete 12-weeks (3 days per week) of a whole-body progressive resistance exercise training program. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 HMB+VitD capsules, twice a day with a meal or snack for a total of 6 capsules per day. Participants will be asked to take capsules  30-60 minutes before resistance exercise. Each capsule contains 500 mg calcium HMB and 333.33 IU Vitamin D for a total of 3.0 g HMB and 2000 IU Vitamin D per day. | Behavioral: Resistance Exercise Training<br>* Participants will complete a 12-week whole-body progressive resistance exercise training program.<br>Dietary Supplement: HMB+VitD<br>* Participants will be given HMB+VitD capsules to consume for 12-weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal Muscle Function - Knee extensor isometric performance | Knee extensor isometric performance will be assessed by a dynamometer. Muscle strength will also be determined by 1 repetition maximum for leg extension, leg curl and leg press exercises. | Change from baseline to after the 12 week intervention | 
| Skeletal Muscle Function - Knee extensor isokinetic performance | Knee extensor isokinetic performance will be assessed by a dynamometer. | Change from baseline to after the 12 week intervention | 
| Skeletal Muscle Function - Fatigue | Knee extensor fatigue will be assessed by a dynamometer. | Change from baseline to after the 12 week intervention | 
| Skeletal Muscle Cross Sectional Area | Skeletal muscle cross sectional area will be assessed via magnetic resonance imaging (MRI). | Change from baseline to after the 12 week intervention | 
| Skeletal Muscle Volume | Skeletal muscle volume will be assessed via magnetic resonance imaging (MRI). | Change from baseline to after the 12 week intervention | 
| Body Composition - Mass | Fat and fat free mass will be measured using by a dual x-ray absorptiometry (DEXA) scan. | Change from baseline to after the 12 week intervention | 
| Body Composition - Percentage | Fat and fat free percent will be measured using by a dual x-ray absorptiometry (DEXA) scan. | Change from baseline to after the 12 week intervention | 
| Skeletal Muscle Mitochondrial Respiration | Mitochondrial respiration will be assessed using high-resolution respirometry in permeabilized muscle fibers. | Change from baseline to after the 12 week intervention | 
| Skeletal Muscle Mitochondrial Hydrogen Peroxide Emissions | Mitochondrial hydrogen peroxide emissions will be assessed using high-resolution fluorometry in permeabilized muscle fibers. | Change from baseline to after the 12 week intervention | 
| Myofiber Size | Cross sectional area of muscle fibers will be evaluated with immunohistochemistry. | Change from baseline to after the 12 week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Density | Bone mineral density will be evaluated by a dual x-ray absorptiometry (DEXA) scan. | Change from baseline to after the 12 week intervention |