October 31, 2012 - Pam R. Taub, MD, a cardiologist and Assistant Clinical Professor in the UC San Diego Department of Medicine, thinks your heart and skeletal muscles could benefit when you eat dark chocolate—just not too much of it. After 5 years of research, including animal studies and one proof-of-concept clinical trial, she and Francisco Villarreal, MD, PhD, have recently embarked on a new clinical study at the CTRI Center for Clinical Research. The trial is designed to assess the effects of epicatechin, a flavanol in dark chocolate, on exercise capacity in subjects with advanced heart failure (HF) and type 2 diabetes mellitus (DM2). Both illnesses are characterized by mitochondrial disruptions, which her prior data suggest are improved with epicatechin administration.
In preclinical studies, rats pretreated with epicatechin and then subjected to ischemia/reperfusion exhibited myocardial infarcts that were much smaller than those in control animals. Beneficial effects of epicatechin were also seen in functional studies, where animals given epicatechin showed enhanced exercise capacity. At the subcellular level, these physiological effects were associated with marked improvements in mitochondrial structure.
In Dr. Taub’s first human clinical study, patients with class III HF, class II/III HF, or DM2 consumed an epicatechin-enriched cocoa plus a small amount of chocolate every day for 3 months. Skeletal muscle biopsies of the quadriceps femoris were carried out both before and after treatment. After treatment, Western blots showed statistically significant stimulation of indicators of mitochondrial biogenesis in all five subjects, and electron microscopy revealed a dramatic improvement in the density and orderly structure of cristae, the submitochondrial structures where oxidative phosphorylation occurs. “The fact that anything could improve in these profoundly ill, deconditioned patients is remarkable,” according to Dr. Taub.
The new clinical study in humans, a randomized, controlled, blinded trial at the CTRI, was begun in September 2012. It will enroll 10 healthy sedentary subjects and 10 subjects with DM2 or stage II HF. The effects of epicatechin and placebo on exercise capacity, morphology of skeletal muscle mitochondria, and quality of life measures will be compared between the two cohorts.
At the start of the study, all subjects will have multiple pretreatment assessments performed: VO2 max (maximal oxygen consumption during exercise), skeletal muscle biopsies, and MRS (a noninvasive MRI of muscle that measures indicators of energy metabolism); plus they will wear accelerometers (which count the number of steps walked) for 2 days, and fill out Quality of Life surveys. In the treatment phase, half of the subjects in each cohort will consume a small amount of epicatechin-enriched dark chocolate daily for 3 months, while the other half in each cohort will eat a placebo resembling dark chocolate, which does not contain epicatechin. Posttreatment, the same assessments that were done at baseline will be repeated, and the data for the two timepoints compared.
Dr. Taub performs the muscle biopsies herself. “Initially patients are apprehensive, but once they get one done, they realize it is not painful and just feel like they may temporarily have a sore muscle, and they agree to do it again.” The chocolate is supplied by the Hershey Center for Health and Nutrition, which sponsors public health initiatives. Clinical support is provided by the CTRI Clinical Research Services. “Vicky Lam and Dan Szpak, RNs at the clinic, are very accommodating, very much collaborative, willing to bend over backwards to implement a procedure that’s new for them,” Dr. Taub says. “We worked out lots of firsts—bicycle ergometry instead of the treadmill type, for example—procedures that other clinics might decline to set up de novo. And Cindy Knott, a Clinical Research Dietitian who helps with the exercise testing, is amazing.”
There are other advantages to working with the CTRI. Dr. Taub reports that the Office of Clinical Trials Administration, which collaborates with the CTRI, completed the contract with Hershey in a month. “The CTRI is fair in terms of cost. They also take care of many things for my patients—patient parking and so forth. I can focus on my research while they take care of the infrastructure.”
So if epicatechin improves mitochondrial biogenesis in skeletal muscles, could we call chocolate a performance-enhancing drug for athletes? “I think you can, actually. But everyone, including sedentary people, could benefit, not just elite athletes.” In fact, Dr. Taub and her colleagues would like to see a pill containing purified epicatechin be made available to consumers, so that they could avoid the less healthy components in commercial chocolate. “The dose-response curve for epicatechin seems to be bell-shaped, unfortunately. In other words, after a certain point, more is not better.” Another future goal is a clinical trial that would more directly examine the effects of epicatechin on the heart (using echocardiography, for example). But for right now, we can feel good about eating two small squares of dark chocolate per day.
About UC San Diego Altman Clinical and Translational Research Institute:
UC San Diego Altman Clinical and Translational Research Institute (ACTRI) is part of a national Clinical and Translational Science Award consortium, led by the National Institutes of Health National Center for Advancing Translational Science. Established in 2010, ACTRI provides infrastructure and support for basic, translational and clinical research throughout the San Diego region to bring discoveries from the laboratory to the bedside, and facilitates training and education of the next generation of researchers. ACTRI carries out its activities in collaboration with institutional and corporate partners and currently has more than 1,500 members.