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LE Magazine February 2008

Cocoa Polyphenols

Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different levels of cocoa powder.

Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder (13, 19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans. In this comparative, double-blind study, we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group) or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and 26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test powders were consumed as a beverage after the addition of hot water, twice each day. Blood samples were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids. Plasma oxidized LDL concentrations decreased in the low-, middle-, and high-cocoa groups compared with baseline. A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or =3.23 mmol/L at baseline. In these subjects, plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the plasma HDL cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups. The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol, an elevation in HDL cholesterol, and the suppression of oxidized LDL.

J Nutr. 2007 Jun;137(6):1436-41

Mechanisms and effects of green tea on cardiovascular health.

Green tea, rich in antioxidant and anti-inflammatory catechins, especially epigallocatechin gallate (EGCG), has been shown to reduce surrogate markers of atherosclerosis and lipid peroxidation, particularly LDL oxidation and malondialdehyde concentrations, in several in vitro, animal, and limited clinical studies. Epidemiological observations in Southeast Asian countries indicate an inverse correlation exists between habitual consumption of green tea beverages and the incidence of cardiovascular events. A few short-term clinical studies have reported its effects in attenuating biomarkers of oxidative stress and inflammation among smokers, and an ability to decrease postprandial lipemia in hypercholesterolemic subjects has also been suggested. However, further investigations are needed to confirm the potential role of green tea beverages and the safety of green tea supplements in reducing body fat, as well as other biomarkers of cardiovascular disease risks.

Nutr Rev. 2007 Aug;65(8 Pt 1):361-75

Tea polyphenols for health promotion.

People have been consuming brewed tea from the leaves of the Camellia sinensis plant for almost 50 centuries. Although health benefits have been attributed to tea, especially green tea consumption since the beginning of its history, scientific investigations of this beverage and its constituents have been underway for less than three decades. Currently, tea, in the form of green or black tea, next to water, is the most widely consumed beverage in the world. In vitro and animal studies provide strong evidence that polyphenols derived from tea may possess the bioactivity to affect the pathogenesis of several chronic diseases. Among all tea polyphenols, epigallocatechin-3-gallate has been shown to be responsible for much of the health promoting ability of green tea. Tea and tea preparations have been shown to inhibit tumorigenesis in a variety of animal models of carcinogenesis. However, with increasing interest in the health promoting properties of tea and a significant rise in scientific investigation, this review covers recent findings on the medicinal properties and health benefits of tea with special reference to cancer and cardiovascular diseases.

Life Sci. 2007 Jul 26;81(7):519-33

Flavonoid intake and cognitive decline over a 10-year period.

In the PAQUID (Personnes Agées Quid) study, the authors prospectively examined flavonoid intake in relation to cognitive function and decline among subjects aged 65 years or older. A total of 1,640 subjects free from dementia at baseline in 1990 and with reliable dietary assessment were reexamined four times over a 10-year period. Cognitive functioning was assessed through three psychometric tests (Mini-Mental State Examination, Benton’s Visual Retention Test, “Isaacs” Set Test) at each visit. Information on flavonoid intake was collected at baseline. A linear mixed model was used to analyze the evolution of cognitive performance according to quartiles of flavonoid intake. After adjustment for age, sex, and educational level, flavonoid intake was associated with better cognitive performance at baseline (p = 0.019) and with a better evolution of the performance over time (p = 0.046). Subjects included in the two highest quartiles of flavonoid intake had better cognitive evolution than did subjects in the lowest quartile. After 10 years’ follow-up, subjects with the lowest flavonoid intake had lost on average 2.1 points on the Mini-Mental State Examination, whereas subjects with the highest quartile had lost 1.2 points. This gradient persisted after adjustment for several other potential confounders. This study raises the possibility that dietary flavonoid intake is associated with better cognitive evolution.

Am J Epidemiol. 2007 Jun 15;165(12):1364-71

Beta-Glucans in promoting health: Prevention against mutation and cancer.

The polysaccharides beta-glucans occur as a principal component of the cellular walls. Some microorganisms, such as yeast and mushrooms, and also cereals such as oats and barley, are of economic interest because they contain large amounts of beta-glucans. These substances stimulate the immune system, modulating humoral and cellular immunity, and thereby have beneficial effect in fighting infections (bacterial, viral, fungal and parasitic). Beta-Glucans also exhibit hypocholesterolemic and anticoagulant properties. Recently, they have been demonstrated to be anti-cytotoxic, antimutagenic and anti-tumorogenic, making them promising candidate as pharmacological promoters of health.

Mutat Res. 2007 Aug 3

The intake of flavonoids and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study.

The role of flavonoids in CVD is still unclear. In this cross-sectional study we assessed the relation between the intakes of twenty-six flavonoids from five subclasses: flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins, and the mean common carotid artery intima-media thickness (CCA-IMT). The study population consisted of 1380 middle-aged eastern Finnish men for whom the mean CCA-IMT examinations were carried out as a part of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). The mean intake of flavonoids was 128.5 (sd 206.7) mg/d and the mean CCA-IMT was 0.78 (sd 0.17) mm. In the lowest quartile of total flavonoid intake the non-adjusted mean CCA-IMT was 0.79 (sd 0.19) mm, while the mean CCA-IMT was 0.76 (sd 0.15) in the highest quartile (P < 0.001). After adjustment for age, variables related to CCA-IMT measurement, history of atherosclerosis, smoking, BMI, diabetes, systolic blood pressure, serum HDL- and LDL-cholesterol, VO2 max, and intakes of alcohol, SFA, folate, vitamins C and E, the total flavonoid intake was inversely associated with the mean CCA-IMT (P = 0.018). Out of different flavonoid subclasses, flavan-3-ols were inversely associated with CCA-IMT (P = 0.025) after statistical adjustment. There was a trend for an inverse association between intake of flavonols and mean CCA-IMT (P = 0.055). We conclude that high intake of flavonoids is associated with decreased carotid atherosclerosis in middle-aged Finnish men.

Br J Nutr. 2007 Oct;98(4):814-8

Apple polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass index.

We performed a randomized double-blind, placebo-controlled study on moderately obese male and female subjects (71 subjects) with a body mass index ranging from 23 to 30 to evaluate the efficacy of 12-week intake of polyphenols extracted from apples and hop bract (600 mg/day). We confirmed that 12-week ingestion of polyphenol-containing capsules significantly decreased total cholesterol and LDL-cholesterol levels. The effects of the apple polyphenol-containing capsules were more marked than those of the hop bract polyphenol-containing capsules. The visceral fat area and the level of adiponectin in the group administered apple polyphenols improved in comparison with the control group. Blood and physical examinations revealed on clinical problems, and no adverse reactions were observed during the ingestion period. These results demonstrate that apple polyphenols regulate fat metabolism in healthy subjects with relatively high body mass index.

J Oleo Sci. 2007;56(8):417-28

Combination therapy of statin with flavonoids rich extract from chokeberry fruits enhanced reduction in cardiovascular risk markers in patients after myocardial infarction (MI).

Recent studies have shown, that chronic flavonoids treatment improves vascular function and cardiovascular remodeling by decreasing superoxide anion production as well as by increasing NO realize from endothelial cells. A progressive decrease in systolic blood pressure and reduction of low-density lipoprotein oxidation (Ox-LDL) has also been reported. However, none of these studies were done in patient with coronary artery disease treated with statins. This was a double-blind, placebo-controlled, parallel trial. Forty-four patients (11 women and 33 men, mean age 66 years) who survived myocardial infarction and have received statin therapy for at least 6 months (80% dose of 40 mg/day simvastatin) were included in the study. The subjects were randomised to receive either 3 x 85 mg/day of chokeberry flavonoid extract (Aronia melanocarpa E) or placebo for a period of 6 weeks. The study extract was a commercially-available (OTC) product of the following declared composition: anthocyans (about 25%), polymeric procyanidines (about 50%) and phenolic acids (about 9%). Compared to placebo (ANOVA and Tukey’s test), flavonoids significantly reduced serum 8-isoprostans (p<0.000) and Ox-LDL levels (p<0.000) (by 38 and 29%, respectively), as well as hsCRP (p<0.007) and MCP-1 (p<0.001) levels (by 23 and 29%, respectively). In addition, significant increase in adiponectin (p<0.03) levels and reduction in systolic and diastolic blood pressure by a mean average of 11 and 7.2 mmHg, respectively were found. CONCLUSION: In view of the fact that chokeberry flavonoids reduce the severity of inflammation, regardless of statins, they can be used clinically for secondary prevention of ischaemic heart disease.

Atherosclerosis. 2007 Oct;194(2):e179-84

Absorption of dietary cholesterol oxidation products and their downstream metabolic effects are reduced by dietary apple polyphenols.

Exogenous and endogenous cholesterol oxidation products (COPs) perturb various metabolic processes, and thereby they may induce various homeostasis-related disorders. Here, we observed that procyanidin-rich dietary apple polyphenol (APP) from unripe apples alleviates the perturbation of lipid metabolism by decreasing the exogenous COP levels in rats. Dietary COPs may be the greatest source of COPs found in the human body. Rats (4 weeks of age) were fed AIN-purified diets containing 0.3% COPs supplemented with 0.5 or 2.5% APP for 3 weeks. Dietary APP alleviated the growth inhibition action of the exogenous COPs. The modulations of the liver lipid profile by COPs remained unchanged. However, serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels increased following the intake of dietary APP. Further, dietary APP inhibited the increase in lipid peroxide levels in the liver and serum by COPs. The activity of hepatic Delta6 desaturase was lowered by dietary APP in a dose-dependent manner, although exogenous COPs generally increased the activity of this enzyme. In keeping with this observation, Delta6 desaturation indices in the phospholipids and cholesteryl esters of the liver and serum lipids were lower in the APP-fed groups than those in the control group. Dietary APP also promoted the excretion of exogenous COPs, cholesterol, and acidic steroids in feces. Therefore, the inhibition of intestinal absorption of COPs may partly contribute to the alleviation of the perturbation of lipid metabolism and lipid peroxidation levels. Thus, APP may be an important removal agent of exogenous toxic material such as COPs contained in processed or fast foods.

Lipids. 2007 Mar;42(2):151-61

Prevention of bone loss by phloridzin, an apple polyphenol, in ovariectomized rats under inflammation conditions.

Aging and sex hormones related changes lead to inflammatory and oxidant conditions, which are involved in the pathogenesis of osteoporosis. Recent studies have suggested that polyphenols may exert a protective effect in such conditions. We assessed the effect of phloridzin (Phlo), a flavonoid exclusively found in apple, on bone metabolism in ovariectomized (OVX) or sham-operated (SH) rats with and without inflammation. Six-month-old Wistar rats were allocated to two equal groups that received either a control diet or a diet supplemented with 0.25% Phlo for 80 days. Three weeks before necropsy, inflammation was induced by subcutaneous injection of talc in 10 animals of each group. At necropsy, ovariectomy decreased both total (T-BMD) and metaphyseal (M-BMD) femoral bone mineral density (P < 0.01). Inflammation conditions, checked by an increase in the spleen weight and alpha1-acid glycoprotein concentration in OVX rats, exacerbated the decrease in T-BMD (g/cm2) (as well as M-BMD) observed in castrated animals (P < 0.05). Daily Phlo intake prevented ovariectomy-induced bone loss in conditions of inflammation as shown by T-BMD and M-BMD (P < 0.05). At the diaphyseal site, BMD was improved by Phlo in OVX rats with or without inflammation (P < 0.05). These results could be explained by changes in bone remodeling as the increased urinary deoxypyridinoline excretion in OVX and OVXinf animals was prevented by the polyphenol-rich diet (P < 0.001), while plasma osteocalcin concentration was similar in all experimental groups. In conclusion, Phlo consumption may provide protection against ovariectomy-induced osteopenia under inflammation conditions by improving inflammation markers and bone resorption.

Calcif Tissue Int. 2005 Nov;77(5):311-8

Modulation of oxidative cell damage by reconstituted mixtures of phenolic apple juice extracts in human colon cell lines.

Diets rich in fruits and vegetables are associated with a lower risk of tumour induction in the intestine and other sites. Apple juice with high amounts of antioxidative phenolics might protect the intestine against reactive oxygen species-mediated cell damage. We investigated to which extent the preventive effectiveness of polyphenolic juice extracts is governed by the amounts of five major constituents (rutin, phloridzin, chlorogenic acid, caffeic acid and epicatechin). In human colon cell lines (Caco-2, HT29), reconstituted mixtures of these phenolics were investigated in comparison to the original juice extracts, originating from cider and table apples. Parameters studied were (oxidative) DNA damage (Comet assay), cellular redox status (dichlorofluorescein assay) and Trolox equivalent antioxidant capacity (TEAC). The TEAC of the reconstituted mixtures was higher compared to the respective original extracts (4.7-7.3 mM vs. 3.6-4.2 mM Trolox). After 24 hour cell incubation, menadione-induced (oxidative) DNA damage was more effectively reduced by the reconstituted mixtures (1-100 microg/mL, 24 h), as compared to the original extracts. In contrast, the cellular ROS level was reduced to a rather similar extent by original extracts and reconstituted mixtures. The results lead to the conclusion that the selected constituents in their authentic proportions substantially account for the antioxidative effectiveness of phenolic apple juice extracts.

Mol Nutr Food Res. 2006 Apr;50(4-5):413-7

Green tea polyphenols: biology and therapeutic implications in cancer.

Multiple lines of evidence, mostly from population-based studies, suggest that green tea consumption is associated with reduced risk of several human malignancies such as cancer and diabetes. Epigallocatechin-3-gallate (EGCG), a major polyphenol found in green tea, is a widely studied chemopreventive agent with potential anticancer activity. Green tea polyphenols inhibit angiogenesis and metastasis, and induce growth arrest and apoptosis through regulation of multiple signaling pathways. Specifically, EGCG regulates expression of VEGF, matrix metalloproteinases, uPA, IGF-1, EGFR, cell cycle regulatory proteins and inhibits NFk B, PI3-K/Akt, Ras/Raf/MAPK and AP-1 signaling pathways, thereby causing strong cancer chemopreventive effects. This review discusses the molecular mechanisms of green tea polyphenols and their therapeutic implications in cancer.

Front Biosci. 2007 Sep 1;12:4881-99

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