Proanthocyanidins (PACs) are a diverse group of plant compounds found in many common foods. They belong to the larger family of polyphenols and are classified as flavonoids, specifically as oligomeric flavan-3-ols. Their presence in foods like cranberries and dark chocolate has generated significant scientific interest. The unique structural features of PACs dictate how they interact with human cells and microbes, leading to distinct effects compared to other dietary compounds.
Classification and Structure of Proanthocyanidins
Proanthocyanidins are polymers formed by linking together smaller flavan-3-ol units, primarily catechin and epicatechin. Oligomeric PACs have a low number of subunits, typically two to ten, while larger chains are called polymers. Structure is categorized based on the chemical bond connecting the subunits, which determines their biological function.
The most common form is B-type PAC, characterized by a single C4-C8 or C4-C6 linkage between adjacent flavan-3-ol units. This single bond creates a relatively flexible chain structure that is widely distributed across the plant kingdom.
A less common structural variant is A-type PAC, which possesses a double linkage. This double bond includes the standard C4-C8 bond and an additional ether linkage (C2-O-C7 or C2-O-C5). This connection creates a more rigid, compact structure, responsible for the unique biological properties of A-type PACs, particularly their anti-adhesion capabilities.
Principal Dietary Sources
PACs are widely distributed, but their concentration and structural type vary significantly by source. B-type PACs are the most prevalent form in the human diet, found in high concentrations in foods like grape seeds, red wine, and apples. Dark chocolate and cocoa beans are also rich sources of B-type procyanidins.
In contrast, A-type PACs are found in fewer sources. The most notable source of A-type PACs is the cranberry, often studied for its distinct health properties. Other sources include cinnamon, peanut skins, litchis, and avocados. PAC concentration can be affected by factors like the specific cultivar, the part of the plant consumed, and the extent of food processing.
Key Biological Mechanisms of Action
PACs exert their effects through several distinct molecular mechanisms, including broad antioxidant activity. Like many polyphenols, PACs scavenge reactive oxygen species (ROS) and neutralize free radicals due to their multiple hydroxyl groups. This action helps to mitigate oxidative stress, a condition linked to cellular damage and the progression of various chronic diseases. The antioxidant effect can also be indirect, involving the inhibition of enzymes like myeloperoxidase (MPO) that generate free radicals.
A specific mechanism, particularly for A-type PACs, is their anti-adhesion property. These molecules prevent pathogenic bacteria and fungi from adhering to the host cell lining. For instance, A-type PACs from cranberries inhibit the adherence of E. coli to the walls of the urinary tract, which is the primary cause of many infections. This is not a bactericidal effect; PACs prevent the initial step of infection by blocking microbial attachment rather than killing the bacteria.
PACs also modulate various cellular signaling pathways and enzyme activities. They interact with inflammatory pathways by hindering the activation of factors like NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells). PACs promote improved vascular health by stimulating nitric oxide (NO) production, which helps blood vessels relax and widen. This modulation allows PACs to influence processes ranging from inflammation and blood pressure regulation to the digestion of carbohydrates and proteins.
Absorption and Bioavailability
The large and complex structure of PACs presents a significant challenge to their absorption in the human body. Due to their high molecular weight and degree of polymerization, intact PACs are generally poorly absorbed in the small intestine. Only the smallest forms, primarily monomers and some oligomers (dimers and trimers), can be absorbed directly through the intestinal wall.
The majority of ingested PACs, particularly the larger polymers, bypass absorption in the small intestine and travel to the colon. It is here that the gut microbiota plays a crucial role in their final metabolic fate. The resident bacteria in the colon break down the large, unabsorbed PAC molecules through fermentation and various enzymatic reactions.
This microbial breakdown converts the complex PACs into smaller, lower molecular weight compounds, such as phenolic acids and valerolactones. These resulting metabolites are significantly more absorbable than the parent compounds and enter the bloodstream, where they can circulate throughout the body. Therefore, many of the systemic biological effects attributed to PAC consumption are likely due to the activity of these microbially generated metabolites rather than the original, intact proanthocyanidins.