Peripheral artery disease affects roughly 230 million people worldwide and arises when plaque accumulation in the arteries impairs the delivery of oxygen-rich blood to the muscles, causing pain with physical activity. A recent study found that cocoa flavanols promote the production of endogenous antioxidants and proteins involved in mitochondrial function in people with peripheral artery disease.

The study involved 16 people with peripheral artery disease who were enrolled in COCOA-PAD, a six-month randomized controlled trial in which participants who received a cocoa beverage containing 15 grams of cocoa (providing 75 milligrams of epicatechin, a flavanol compound) daily showed marked improvements in walking performance and less pain with activity. Researchers examined muscle samples taken before and after the trial to study changes in muscle fibers, endogenous antioxidants (heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1), and energy-related proteins.

They found that participants who received the cocoa beverage had higher levels of endogenous antioxidants, correlating with less muscle damage. They also had higher levels of UQCRC2, a protein critical for energy production in the mitochondria.

These findings suggest that cocoa flavanols promote the synthesis of endogenous antioxidants and proteins involved in energy production and point toward a mechanism for the beneficial effects observed in COCOA-PAD. Because heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1 are targets of nuclear factor erythroid 2-related factor 2 (Nrf2), the investigators posited that the mechanism driving the beneficial effects of cocoa flavanol supplementation is Nrf2 activation.

Nrf2 is a protein typically found in the cytoplasm of mammalian cells. Nrf2 can relocate to the nucleus, where it regulates the expression of hundreds of antioxidant and stress response proteins that protect against oxidative damage triggered by injury and inflammation. Although this study found that cocoa induces Nrf2, one of the most robust inducers of Nrf2 is sulforaphane, a compound derived from broccoli. Learn more about sulforaphane and Nrf2 in this clip featuring Dr. Jed Fahey.