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

Not Applicable

Completed

• Conditions: Heart Failure; Type 2 Diabetes
• Interventions: Dietary Supplement: Epicatechin-enriched dark chocolate; Other: Low-epicatechin dark chocolate

• Registration Number: NCT01671514
• Lead Sponsor: University of California, San Diego

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.)

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-08-20
• Study First Submitted QC: 2012-08-22
• Study First Posted: 2012-08-23
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-01
• Last Update Posted: 2015-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sedentary	Low-epicatechin dark chocolate	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.
Heart failure/diabetes	Low-epicatechin dark chocolate	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.
Sedentary	Epicatechin-enriched dark chocolate	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.
Heart failure/diabetes	Epicatechin-enriched dark chocolate	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.

Primary Outcome Measures

Name	Time	Method
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.
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

Trial Locations

Locations (1)

University of California, San Diego; 🇺🇸 La Jolla, California, United States