Heart Failure, Type 2 Diabetes
Conditions
Keywords
mitochondrial biogenesis, skeletal muscle, epicatechin
Brief summary
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 1. Patients with heart failure (HF) and type 2 diabetes (DM2) and 2. 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
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.)
Interventions
DIETARY_SUPPLEMENTEpicatechin-enriched dark chocolate
For experimental purposes, subjects will take one square of epicatechin-enriched dark chocolate per day for 90 days.
OTHERLow-epicatechin dark chocolate
As a placebo control, subjects will take 1 square of low-epicatechin chocolate per day for 90 days.
Sponsors
The Hershey Company
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in exercise capacity | Baseline and 3 months | Objectively evaluate exercise capacity through cycle ergometry to measure VO2 max. |
| Change from baseline in skeletal muscle metabolism | Baseline and 3 months | The change in skeletal muscle metabolism will be evaluated by magnetic resonance spectroscopy |
| Change from baseline in pre-specified biomarker levels in blood, skeletal muscle, and urine | Baseline and 3 months | Skeletal muscle biopsies and blood draws will be performed to obtain experimental samples. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in quality of life, health, and nutrition questionnaires | Baseline and 3 months | Specific questionnaires utilized include SF-36 questionnaire, Morisky Medication Adherence Scale (MMAS-8) questionnaire, the Minnesota Living with Heart Failure scale (MLHFQ), the Physical Activity Enjoyment Scale (PACES), the Leisure Time Exercise questionnaire (LTE), the Multidimensional Fatigue Symptom Inventory (MFSI) and the Block Questionnaires for Dietary Fat Screening and Fruit/Vegetable/Fiber Screening |
Countries
United States
Outcome results
None listed