Bioactivity of a flavanol-rich lychee fruit extract in adipocytes and its effects on oxidant defense and indices of metabolic syndrome in animal models.

Many polyphenolic compounds are poorly digested, and have low bioavailability due to their long chain lengths and chemical composition. A processed, flavanol-rich lychee fruit extract (FRLFE) that is higher in flavanol monomers, dimer and trimers than its unprocessed counterpart, was tested in a variety of models. First, mature visceral adipocytes were treated with 0, 3, 10 or 30 microg/mL FRLFE (day 6-8). Compared with the controls, the treated cells had lower triglyceride concentrations, less lipid accumulation and a smaller lipid droplet size. Adiponectin release was significantly greater in cells receiving 3 or 10 microg/mL FRLFE than in the controls. Second, rats given a single dose of 50 or 100 mg/kg FRLFE had significant increases in plasma (-)-epicatechin, 3'-O-methyl-(-)-epicatechin, and (+)-catechin levels, peak values were at approximately 2 h and appreciable concentrations were still detected at 6 h. Rats supplemented daily for 1 week with 50 or 100 mg/kg FRLFE had significantly elevated metabolite concentrations. In response to an oxidative stress, erythrocyte membrane integrity was significantly improved in the 100 mg/kg FRLFE group. Third, 7-month-old mice fed a 200 mg/kg FRLFE diet for 10 months showed a significant decrease in glucose, triglyceride and lipid peroxide levels compared with mice fed a control diet. Collectively, these results support the concept that the flavanols present in FRLFE are well absorbed and bioactive.

Effects of a flavonol-rich diet on select cardiovascular parameters in a Golden Syrian hamster model.

The concept that the consumption of a diet rich in flavonoids can be associated with a reduced risk for cardiovascular disease is becoming increasingly accepted. In the present study we investigated the effects of the following four diets on blood pressure and cholesterol ester levels in hypercholesterolemic Golden Syrian hamsters: a high-fat, high-cholesterol diet (HFHC); a HFHC with 2% cranberry concentrate powder (HFHC+CE); a HFHC with 0.1% rutin (HFHC+Rutin); and a HFHC with 30 mg/kg vitamin E (HFHC+Vit.E). Diets were fed for either 12 or 20 weeks. Over the experimental period, heart rate and blood pressure measurements increased in the animals fed HFHC and HFHC+Vit.E; in contrast, these measurements were not increased in the animals fed HFHC+CE and HFHC+Rutin. Mesenteric and total abdominal fat were significantly lower in the animals fed HFHC+Rutin than in animals fed the other three diets. Ratios of plasma high-density lipoprotein cholesterol (HDL-C) to very-low-density lipoprotein cholesterol and of plasma HDL-C to low-density lipoprotein cholesterol were significantly higher in animals consuming HFHC+Vit.E than in animals fed the other three diets. Aortic cholesteryl ester levels were significantly lower in animals fed HFHC+CE, HFHC+Rutin, and HFHC+Vit.E at 20 weeks than in the animals fed HFHC. Fasting blood glucose concentrations were significantly lower in animals fed HFHC+Rutin and HFHC+Vit.E, and glucose clearance rates improved in animals fed HFHC+Rutin compared to animals fed the other three diets. Results obtained from this study support the concept that the chronic consumption of a flavonoid-rich diet can be beneficial with respect to cardiovascular health.

Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial.

OBJECTIVES: Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients. BACKGROUND: Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk. METHODS: In a feasibility study with 10 diabetic patients, we assessed vascular function as flow-mediated dilation (FMD) of the brachial artery, plasma levels of flavanol metabolites, and tolerability after an acute, single-dose ingestion of cocoa, containing increasing concentrations of flavanols (75, 371, and 963 mg). In a subsequent efficacy study, changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day, thrice-daily dietary intervention with either flavanol-rich cocoa (321 mg flavanols per dose) or a nutrient-matched control (25 mg flavanols per dose). Both studies were undertaken in a randomized, double-masked fashion. Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites, respectively. RESULTS: A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD (at 2 h: from 3.7 +/- 0.2% to 5.5 +/- 0.4%, p < 0.001). A 30-day, thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30% (p < 0.0001), while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study. Treatment was well tolerated without evidence of tachyphylaxia. Endothelium-independent responses, blood pressure, heart rate, and glycemic control were unaffected. CONCLUSIONS: Diets rich in flavanols reverse vascular dysfunction in diabetes, highlighting therapeutic potentials in cardiovascular disease.

Platelet reactivity in male smokers following the acute consumption of a flavanol-rich grapeseed extract.

Epidemiological studies suggest that a high dietary intake of flavanols, a subclass of flavonoids, is associated with reduced risk of vascular disease. Clinical studies have also shown that the consumption of certain flavanol-rich foods (e.g., cocoa, tea, red wine), as well as intake of the individual flavanol (-)-epicatechin, can result in improvement in a number of parameters associated with vascular disease, including improved endothelial function, reduced platelet reactivity, and reduced oxidative stress. The present study assessed the effects of a flavanol-rich supplement on platelet reactivity and plasma oxidant defense in a group of smokers, a population at an elevated risk for vascular disease. Male smokers were randomly assigned to a placebo (n = 10) or a flavanol-rich grapeseed extract (FRGSE; n = 13) group, and after an overnight fast, blood samples were collected before and at 1, 2, and 6 hours following consumption of the placebo or supplement. The FRGSE supplement, but not the placebo, significantly decreased ADP-stimulated platelet reactivity at 1, 2, and 6 hours following intake (P < .05) compared to baseline levels. Similarly, the supplement, but not the placebo, decreased epinephrine-stimulated platelet reactivity 2 hours following consumption. Plasma antioxidant capacity (total radical trapping antioxidant potential), lipid oxidation (plasma thiobarbituric acid-reactive substances), and serum uric acid concentrations were not affected in either group. Thus smokers may obtain some health benefits from the consumption of certain flavanol-rich foods, beverages, and supplements.

Enzymatic O-methylation of flavanols changes lag time, propagation rate, and total oxidation during in vitro model triacylglycerol-rich lipoprotein oxidation.

3'-O-Methyl derivatives of flavan-3-ols, (+)-catechin (C), (-)-epicatechin (EC), and (-)-catechin gallate (CG) were prepared enzymatically. Hexanal (EC and CG family, 5 mmol/L) and conjugated diene (C and EC family, 0.25-10 mmol/L) formation following CuSO4-mediated triacylglycerol-rich lipoprotein oxidation was measured. All EC and CG compounds significantly reduced hexanal formation (p < 0.02). O-Methylation improved the ability of CG (more polar) while reducing the ability of EC (less polar) to limit hexanal formation. 3'-O-methyl EC was 18% (p < 0.001) and 4'-O-methyl 65% (p < 0.001) less able than EC to suppress hexanal formation. At >1 micromol/L all EC and C compounds significantly increased lag time. Parent compounds were more effective (> 4-fold increase) than metabolites (1.5-fold increase). Parent compounds did not influence propagation rate (DeltaOD/min). At >1 mmol/L O-methylated EC and C reduced propagation by 20-40% (p < 0.01). Notably, at 0.25 mmol/L O-methylated EC and C increased propagation rates 22% (p < 0.01) despite prolonging lag time.

Walnuts reduce aortic ET-1 mRNA levels in hamsters fed a high-fat, atherogenic diet.

Walnut consumption is associated with reduced coronary vascular disease (CVD) risk; however, the mechanisms responsible remain incompletely understood. Recent clinical studies suggested that these mechanisms involve non-plasma lipid-related effects on endothelial function. Male Golden Syrian hamsters (12 groups, n=10-15) were fed for 26 wk atherosclerotic, high-fat, hyperlipidemic diets with increasing concentrations of whole walnuts (61-150 g/kg diet), or alpha-tocopherol (alpha-T, 8.1-81 mg/kg diet) and single diets with either walnut oil (32 g/kg diet) or pure gamma-tocopherol (gamma-T; 81 mg/kg diet) added. Aortic endothelin 1 (ET-1), an important endothelial regulator, was assayed as mRNA. Aortic cholesterol ester (CE) concentration along with other vascular stress markers (Cu/Zn and Mn superoxide dismutase, biliverdin reductase) and plasma lipid concentrations were determined. Hyperlipidemia (plasma LDL cholesterol approximately 6 times normal) occurred in all groups. Aortic CE concentration, a measure of atherosclerotic plaque, was highest in the lowest alpha-T only group and declined significantly with increasing alpha-T. The aortic CE of all walnut groups was decreased significantly relative to the lowest alpha-T only group but showed no dose response. The diets did not produce changes in the other vascular stress markers, whereas aortic ET-1 mRNA levels declined dramatically with increasing dietary walnuts (to a 75% reduction in the highest walnut content group compared with the lowest alpha-T group) but were unaltered in the alpha-T groups or gamma-T group. The study results are consistent with those of human walnut feeding studies and suggest that the mechanisms underlying those results are mediated in part by ET-1-dependent mechanisms. The contrasting results between the alpha-tocopherol or gamma-tocopherol diets and the walnut diets also make it unlikely that the non-plasma lipid-related CVD effects of walnuts are due to their alpha-tocopherol or gamma-tocopherol content. Finally, the results indicate that the walnut fat compartment is a likely location for the components responsible for the reduced aortic CE concentration.

Influence of cocoa flavanols and procyanidins on free radical-induced human erythrocyte hemolysis.

Cocoa can be a rich source of antioxidants including the flavan-3-ols, epicatechin and catechin, and their oligomers (procyanidins). While these flavonoids have been reported to reduce the rate of free radical-induced erythrocyte hemolysis in experimental animal models, little is known about their effect on human erythrocyte hemolysis. The major objective of this work was to study the effect of a flavonoid-rich cocoa beverage on the resistance of human erythrocytes to oxidative stress. A second objective was to assess the effects of select purified cocoa flavonoids, epicatechin, catechin, the procyanidin Dimer B2 and one of its major metabolites, 3'-O-methyl epicatechin, on free radical-induced erythrocyte hemolysis in vitro. Peripheral blood was obtained from 8 healthy subjects before and 1, 2, 4 and 8h after consuming a flavonoid-rich cocoa beverage that provided 0.25g/kg body weight (BW), 0.375 or 0.50g/kg BW of cocoa. Plasma flavanol and dimer concentrations were determined for each subject. Erythrocyte hemolysis was evaluated using a controlled peroxidation reaction. Epicatechin, catechin, 3'-O-methyl epicatechin and (-)-epicatechin-(4beta > 8)-epicatechin (Dimer B2) were detected in the plasma within 1 h after the consumption of the beverage. The susceptibility of erythrocytes to hemolysis was reduced significantly following the consumption of the beverages. The duration of the lag time, which reflects the capacity of cells to buffer free radicals, was increased. Consistent with the above, the purified flavonoids, epicatechin, catechin, Dimer B2 and the metabolite 3'-O-methyl epicatechin, exhibited dose-dependent protection against AAPH-induced erythrocyte hemolysis at concentrations ranging from 2.5 to 20 microM. Erythrocytes from subjects consuming flavonoid-rich cocoa show reduced susceptibility to free radical-induced hemolysis (p < 0.05).