Effects of Dark Chocolate on Exercise Capacity, and Mitochondrial Structure and Function

Study Overview
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Brief Summary
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The major goal of this study is to characterize the ability of dark chocolate enriched in epicatechin (a component of dark chocolate) to improve the structural and functional features of mitochondria in two groups Patients with heart failure (HF) and type 2 diabetes (DM2) and Normal yet sedentary individuals with impaired baseline exercise capacity (as assessed by VO2 max) We propose that a 3 month treatment with dark chocolate will lead to a significant improvement in exercise capacity which will be secondary to the improvement in skeletal muscle structure from epicatechin.

Detailed Description
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The flavanol epicatechin (which is derived from cocoa and has no known toxicity in humans) has been shown in clinical trials to increase levels of nitric oxide (NO) as assessed by flow-mediated dilation (FMD) in the brachial artery and measurements of circulating NO in plasma. NO is thought to be an activator of PGC-1 alpha [PPAR (peroxisome proliferator-activated receptor) alpha coactivator 1] which stimulates mitochondrial biogenesis. In both patients with heart failure and diabetes there is nitric oxide deficiency and mitochondrial dysfunction. In our proposed double-blinded placebo controlled clinical trial, we will test the hypothesis that chronic administration of epicatechin to patients with both heart failure and diabetes will increase levels of NO and PGC-1 alpha leading to increased mitochondrial biogenesis and improved mitochondrial function. We believe similar changes will occur in sedentary individuals. In a preliminary study with 5 patients with heart failure and diabetes (conducted under UCSD IRB protocol number #090688) we have shown that epicatechin enriched dark chocolate improves mitochondrial structure (Taub PR, Ramirez-Sanchez I, Ciaraldi TP, et al. Alterations in Skeletal Muscle Indicators of Mitochondrial Structure and Biogenesis in Patients with Type 2 Diabetes and Heart Failure: Effects of Epicatechin Rich Cocoa. Clin Transl Sci. 2011;5(1):43-47.)

Official Title
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Effects of Epicatechin-enriched Dark Chocolate on Mitochondrial Function and Exercise Capacity in Patients With Both Diabetes and Heart Failure and in Sedentary Individuals

Conditions
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Heart Failure, Type 2 Diabetes

Intervention / Treatment
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* Dietary Supplement: Epicatechin-enriched dark chocolate
* Other: Low-epicatechin dark chocolate


Participation Criteria
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Eligibility Criteria
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Healthy, sedentary individuals: Inclusion Criteria: Healthy, inactive individuals BMI 27-32 Exclusion Criteria: Smoking or quit smoking less than 1 year prior to enrollment Currently taking Coumadin or Pradaxa. Heart failure and diabetes patients: Inclusion Criteria: Medically diagnosed with heart failure and diabetes No significant HbA1C fluctuations in past 6 months Exclusion Criteria: Currently taking Insulin Currently taking Coumadin or Pradaxa. Smoking or quit smoking less than 1 year prior to enrollment

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sedentary<br>The sedentary arm will be randomly assigned to either epicatechin-enriched dark chocolate or low-epicatechin dark chocolate as a placebo. Participants will take one square of chocolate per day for 90 days. | Dietary Supplement: Epicatechin-enriched dark chocolate<br>* For experimental purposes, subjects will take one square of epicatechin-enriched dark chocolate per day for 90 days.<br>Other: Low-epicatechin dark chocolate<br>* As a placebo control, subjects will take 1 square of low-epicatechin chocolate per day for 90 days.<br>|
| Experimental: Heart failure/diabetes<br>The heart failure/diabetes arm will be randomly assigned to either epicatechin-enriched dark chocolate or low-epicatechin dark chocolate as a placebo. Participants will take one square of chocolate per day for 90 days. | Dietary Supplement: Epicatechin-enriched dark chocolate<br>* For experimental purposes, subjects will take one square of epicatechin-enriched dark chocolate per day for 90 days.<br>Other: Low-epicatechin dark chocolate<br>* As a placebo control, subjects will take 1 square of low-epicatechin chocolate per day for 90 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in exercise capacity | Objectively evaluate exercise capacity through cycle ergometry to measure VO2 max. | Baseline and 3 months | 
| Change from baseline in skeletal muscle metabolism | The change in skeletal muscle metabolism will be evaluated by magnetic resonance spectroscopy | Baseline and 3 months | 
| Change from baseline in pre-specified biomarker levels in blood, skeletal muscle, and urine | Skeletal muscle biopsies and blood draws will be performed to obtain experimental samples. | Baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mitochondrial biogenesis, skeletal muscle, epicatechin