The pharmacodynamics of cocoa are very complex, so I will focus on two major classes of constituents—the methylxanthines, which include caffeine, and the proanthocyanidins, which are high-molecular weight polyphenols. The former underpin stimulant effects; the latter serve to improve gut microbiota composition and improve metabolic and cellular health. Taken regularly, cocoa products can lower blood pressure, improve immune function and reduce the risk of metabolic syndrome. These health benefits are ascribed to proanthocyanidins, large chains of polyphenols. These compounds have attracted considerable interest in nutrition and integrative medicine due to their cardioprotective, antiinflammatory, antidiabetic and anticancer actions. Food sources include wine, fruits, cocoa, nuts, seeds and botanical medicines; apples, chocolate and grapes are the primary sources in the American diet.
Most proanthocyanidins are too large to be absorbed. It has been proven that they are not broken down in the body into their monomeric units as if they were beads falling off of a necklace. So, how do these large molecules exert their cardioprotective, chemopreventive and neuroprotective actions? Only small proanthocyanidins are able reach the circulation intact, but plasma accumulation has been reported at low nanomolar concentrations at best. These levels are considered to be far too modest to account for known therapeutic effects.
It turns out that the vast majority of proanthocyanidins from cocoa, or from any food, never leave the gut—they are simply too large to be absorbed. Thus, many of their mechanisms are believed to be confined to local effects within the digestive tract. Here, they modify gut microbial populations to relay broad systemic signals that support prevention of disease. Indeed, the clinical indications for probiotic therapy (e.g. oral supplementation of Lactobacilli and Bifidobacteria) have begun to overlap the range of cardiovascular, metabolic and antiiflammatory utility of cocoa. In simple terms, cocoa is a prebiotic and synbiotic. Preliminary studies suggest its effects may be potentially selective to the effect of favoring the survival of friendly bacteria and attenuating the proliferation of certain unwanted species.
Historically, these benefits have been sought in the use of first-generation prebiotics such as oligosaccharides and fibers. These preparations are fraught with dose-limiting intolerances at effective doses and can be indecisive as to favor the good or the bad microbial residents of the gut.
Proanthocyanidins and other high-molecular weight polyphenols (collectively known as tannins) are the next generation of prebiotics. They are effective at low doses, are well tolerated, are easily obtained from readily available foods, such as cranberries, cocoa, wine, and pomegranate. And yes, they appear to be selective, supporting the the “good” bacteria while discouraging the not-so-good varieties.
Integrative Pharmacology 