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.
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.)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
DOUBLE
Enrollment
21
For experimental purposes, subjects will take one square of epicatechin-enriched dark chocolate per day for 90 days.
As a placebo control, subjects will take 1 square of low-epicatechin chocolate per day for 90 days.
University of California, San Diego
La Jolla, California, United States
Change from baseline in exercise capacity
Objectively evaluate exercise capacity through cycle ergometry to measure VO2 max.
Time frame: Baseline and 3 months
Change from baseline in skeletal muscle metabolism
The change in skeletal muscle metabolism will be evaluated by magnetic resonance spectroscopy
Time frame: 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.
Time frame: Baseline and 3 months
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