Modulating Phenolic Bioaccessibility and Glycemic Response of Starch-Based Foods in Wistar Rats by Physical Complexation between Starch and Phenolic Acid.

This study assessed the impact of caffeic and ferulic acid complexation with maize amylopectin or potato starch on glycemic parameters. In comparison to starch-phenolic mixtures, starch-phenolic complexes resulted in significant modification of phenolic bioaccessibility and cellular uptake (p < 0.05). In addition, glucose release from in vitro digestion of starch was modestly reduced in the complexes compared to native starch alone (21.2-26.8 versus 29.8-30.5 mM). Furthermore, intestinal glucose transport, assessed in Caco-2 cell monolayers, was not affected by the presence of complexes (82.4-124 versus 100% at 90 min). However, a reduced glycemic response was evident in a Wistar rat model, with significant reduction in 240 min of blood glucose area under the curve following oral administration of the potato starch-ferulic acid complex compared to native potato starch (26 170 ± 556 versus 28 951 ± 486 mg min dL-1; p < 0.001). These alterations were attributed to complexation-induced resistant starch formation and phenolic entrapment, providing an alternative mechanistic approach to modulate glycemic properties of starch-based foods.

Flavanol supplementation protects against obesity-associated increases in systemic interleukin-6 levels without inhibiting body mass gain in mice fed a high-fat diet.

Weight gain and obesity are associated with increased levels of proinflammatory cytokines. Studies have demonstrated the ability of dietary flavanols to reduce the severity of metabolic derangements due to high-fat (HF) feeding. The degree of polymerization of the flavanols appears to play a role in determining the extent of these protective effects. This study evaluated the preventative effects of grape seed and pine bark flavanol supplementation, with significantly different flavanol degree of polymerization, in the context of an HF diet. For 13 weeks, mice were given 35 mg/kg body weight per day grape seed or pine bark as part of an HF diet and compared to mice fed a low-fat diet and control HF diet. All flavanol-supplemented groups and the HF control incurred significantly higher weight gain compared to the lean control, and the grape seed group gained significantly more weight than the HF control. Increased weight gain of treatment groups was likely caused by hyperphagia. Despite lack of improvements to weight gain and glycemic control, it was observed that all flavanol treatment groups were able to significantly reduce interleukin-6 compared to HF control. The grape seed group, which gained the most weight overall, also exhibited the lowest levels of interleukin-6 compared to other groups. Overall, low-dose flavanol extract supplementation, regardless of mean degrees of polymerization, blunted cytokine production despite increased weight gain. This obesity-independent effect suggests flavanols may be used as complementary interventions to ameliorate increased inflammatory tone in the contexts of obesity and diabetes. Furthermore, flavanol-induced hyperphagia may have use for attenuation of cachexia.

Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults.

The gut microbiome metabolizes choline and carnitine to release trimethylamine (TMA), which subsequently undergoes hepatic conversion to trimethylamine N-oxide (TMAO). Elevated TMAO levels are associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could reduce intestinal TMA production and lower circulating TMAO. However, this hypothesis has never been tested in humans. A secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols in a randomized crossover design while consuming a controlled diet. These subjects generally had elevated TMAO levels (∼5 µM) compared to levels previously measured in healthy subjects (∼1 µM). None of the interventions significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. Traditional physiological characteristics do not appear to predict TMAO responsiveness to flavanol interventions. However, African-American subjects appeared less responsive compared to non-Hispanic white subjects for both green tea and high cocoa treatments, and female subjects appeared less responsive than males for the high cocoa treatment. The present results suggest that a short-term flavanol intervention does not generally reduce fasting TMAO levels in subjects with elevated circulating TMAO.

Alterations to metabolically active bacteria in the mucosa of the small intestine predict anti-obesity and anti-diabetic activities of grape seed extract in mice.

Epidemiological and clinical studies suggest that grapes and grape-derived products may reduce the risk for chronic disease. Grape seed extract specifically has been gaining interest due to its reported ability to prevent weight gain, moderate hyperglycemia, and reduce inflammation. The purpose of this study was to examine the long-term effects of two doses of grape seed extract (10 and 100 mg kg-1 body wt per d in mice) on markers of metabolic syndrome in the context of a moderately high-fat diet. After 12 weeks, the lower dose of grape seed extract was more effective at inhibiting fat gain and improving glucose tolerance and insulin sensitivity. Neither the high fat diet nor grape seed extract altered skeletal muscle substrate metabolism. Most interestingly, when examining the profile of metabolically active microbiota in the mucosa of the small intestine, cecum, and colonic tissue, grape seed extract seemed to have the most dramatic effect on small intestinal tissue, where the population of Firmicutes was lower compared to control groups. This effect was not observed in the cecal or colonic tissues, suggesting that the main alterations to gut microbiota due to flavan-3-ol supplementation occur in the small intestine, which has not been reported previously. These findings suggest that grape seed extract can prevent early changes in glucose tolerance and alter small intestinal gut microbiota, prior to the onset of skeletal muscle metabolic derangements, when grape seed extract is consumed at a low dose in the context of a moderately high fat diet.

Oligomeric cocoa procyanidins possess enhanced bioactivity compared to monomeric and polymeric cocoa procyanidins for preventing the development of obesity, insulin resistance, and impaired glucose tolerance during high-fat feeding.

There is interest in the potential of cocoa flavanols, including monomers and procyanidins, to prevent obesity and type-2 diabetes. Fermentation and processing of cocoa beans influence the qualitative and quantitative profiles of individual cocoa constituents. Little is known regarding how different cocoa flavanols contribute to inhibition of obesity and type-2 diabetes. The objective of this study was to compare the impacts of long-term dietary exposure to cocoa flavanol monomers, oligomers, and polymers on the effects of high-fat feeding. Mice were fed a high-fat diet supplemented with either a cocoa flavanol extract or a flavanol fraction enriched with monomeric, oligomeric, or polymeric procyanidins for 12 weeks. The oligomer-rich fraction proved to be most effective in preventing weight gain, fat mass, impaired glucose tolerance, and insulin resistance in this model. This is the first long-term feeding study to examine the relative activities of cocoa constituents on diet-induced obesity and insulin resistance.

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats.

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified.