Influence of dietary polyphenols on carbohydrate intestinal digestion and absorption

Both epidemiological and clinical evidence support the notion that polyphenol rich foods and beverages may modify glycemic response, glucose homeostasis and subsequent risk of Type-2 diabetes. In vitro evidence typically derived from experiments with pure phenolics and phenolic rich extracts have pointed to this benefit being associated with two potential mechanisms: (1) the ability of specific polyphenolics to inhibit carbohydrate digestion (amylase and glucosidase) and (2) polyphenolic inhibition of intestinal glucose transport. While the high potential of these activities is evident, little is actually known regarding the extent to which these benefits are extendable to the actual food matrix these phenolics are naturally present in. Further, the extent to which co-consumption of polyphenol rich foods may actually result in decreased glycemic response from a mixed meal remains mostly unknown. Considering these limitations, additional insights are required in order to advance knowledge on the benefits of polyphenolics on glucomodulatory mechanisms and translation of these insights into meaningful recommendations and products for consumers. With this in mind, the objectives of these studies were to determine the extent to which phenolic-rich foods (grapes and potatoes) exert glucomodulatory properties in model food systems using in vitro and in vivo assessments. First, mechanisms associated with polyphenol rich extracts or model foods on carbohydrate intestinal digestion and glucose transport were investigated in vitro using a three-stage in vitro digestion model coupled to the Caco-2 human intestinal cell model. Components of this model used individually or in combination allowed for assessment of the two main mechanistic steps in phenolic modulation of glycemic response (starch digestion and glucose transport) in the context of interactions with bioaccessible phenolics. Additionally, the ability of the coupled in vitro digestion/Caco-2 model to predict in vivo outcomes was assessed. The first study compared the ability of 100% Niagara or Concord grape juice (GJ) phenolics to modify carbohydrase activity and intestinal glucose transport relative to a sugar sweetened beverage. While grape juices remain a major dietary source of phenolics, they are also well recognized to be naturally high in sugar content. Insights into the ability of natural fruit phenolics to modify glycemic response of grape juice were investigated in vitro. Also, in consideration that 100% GJ is consumed with meals, the extent to which modulation of carbohydrate digestion and intestinal absorption by GJ phenolics can be extended to a carbohydrate rich meal was evaluated. In the first experiment, inhibition of α-amylase and α-glucosidase by GJ extracts (300 and 500 μM total phenolics) and ability of GJ extracts (10 to 100 μM total phenolics) to modulate labelled glucose and fructose transport across Caco-2 intestinal cell monolayers compared to a phenolic-free control were determined. GJ extracts decreased α-glucosidase, but not α-amylase activity at both concentrations tested. Further, glucose and fructose transport were significantly (p\u3c0.05) decreased in a dose-dependent manner by Niagara and Concord GJ extracts. In a second experiment, GJs and phenolic-free control beverages were co-digested in vitro with a starch-rich model meal. Resulting aqueous digesta (AQ) from both experiments were used to assess impact of bioaccessible GJ phenolics on carbohydrate digestion and glucose transport. Concord and Niagara GJs significantly decreased in vitro gastrointestinal digestion of carbohydrate from model meal compared with a sugar-matched control. Further, d7-glucose transport from AQ fraction of GJ and co-digested GJ and carbohydrate-rich meal across Caco-2 human intestinal cell monolayers was significantly decreased compared to phenolic-free sugar-sweetened control. The second study evaluated potential for phenolics from starch rich white, purple, or red potatoes to modulate carbohydrate digestion or glucose transport in a Caco-2 intestinal cell model. Potato phenolic extracts (300 μM) had no impact on α-amylase activity, and marginally decreased α-glucosidase activity. However, potato phenolic extracts (25-100μM) did decrease d7-glucose transport compared to phenolic-free control. Interestingly, whole potato phenolic extracts reduced glucose transport to a greater extent compared to those from potato peel. To determine if results from aforementioned in vitro assays are predictive of effects in vivo, a pilot clinical study (n=11) was completed to assess differences in acute blood glucose response and gastric emptying following consumption of phenolic-rich purple and red potato chips compared to white potato chips (50g available carbohydrate) containing lower level of total phenolics. Blood glucose levels were measured for up to two hours. Peak blood glucose levels were lower for pigmented chips, especially purple chips, compared to white chips without any significant changes in gastric emptying. These results suggest that potato phenolics may play a role in modulation of intestinal glucose transport and that these effects are translatable to consumer products such as potato chips. Taken together, these data support the notion that phenolics intrinsic to select foods have the ability to modify glycemic response through alteration of glucose transport and to a certain extent starch digestion. Therefore, it is likely that observed benefits associated with consumption of phenolic-rich foods and 100% fruit juices, as a part of an overall healthy diet, may be associated with the ability of intrinsic and bioaccessible phenolics to modify glycemic response. Future research that focuses on hypoglycemic effects of phenolic-rich foods should be larger scale and should evaluate a greater variety of phenolic-rich foods in order to better understand the extent to which phenolic class and food matrix impact hypoglycemic effects. Regarding meal-effects, a pilot clinical study should be completed to validate in vitro results and to provide information as to what degree various types of meal patterns alter glycemic effects of phenolic-rich foods. Such information can be leveraged in the development of phenolic-rich food products that have post-prandial glycemic effects and for making recommendations of dietary choices which may result in improved glucose homeostasis