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Cardiovascular Health and Anti-inflammatory Benefits

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Cranberry flavonoids, atherosclerosis and cardiovascular health

Posted
Authors
Reed J
Journal
Crit Rev Food Sci Nutr 42(3 Suppl):301-16
Abstract

Atherosclerosis is the deposition of plaques containing cholesterol and lipids in arterial walls. Atherosclerosis causes cardiovascular disease that lead to heart attacks and stroke. Mortality from these diseases is the leading cause of death in the U.S. Atherogenisis starts with the uptake of oxidized LDL by endothelial macrophages, the accumulation of foam cells in the intima of the artery and the formation of fatty streaks. Research indicates that consumption of flavonoids in foods and beverages may decrease the risk of atherosclerosis. In vitro and in vivo experiments with flavonoids demonstrate that flavonoids are dietary antioxidants and inhibit LDL oxidation, inhibit platelet aggregation and adhesion, inhibit enzymes involved in lipid and lipoprotein metabolism that affect the immune response to oxidized LDL and their uptake by endothelial macrophages, may induce endothelium-dependent vassorelaxation, and may increase reverse cholesterol transport and decrease total and LDL cholesterol. Cranberries contain both hydroxycinnamic acids and flavonoids. The cranberry flavonoids belong to three groups: anthocyanins, flavonols, and proanthocyanidins. This article reviews the literature on the effects of flavonoids on atherosclerosis with an emphasis on the potential effects of the flavonols and proanthocyanidins in cranberries.

Evidences of the cardioprotective potential of fruits: the case of cranberries.

Posted
Authors
Ruel G, Couillard C
Journal
Mol Nutr Food Res 51(6):692-701
Abstract

Eating a healthy balanced diet, is one of the most important and relevant ways to delay and prevent various health complications including cardiovascular disease (CVD). Among the nutritional factors that have been investigated in recent years, dietary fat intake may be the one that has been most targeted. However, there is also clear epidemiological evidence that increased fruits and vegetables intake can significantly reduce the risk of CVD, an effect that has been suggested to be resulting to a significant extent, from the high polyphenol content of these foods. Numerous polyphenolic compounds such as flavonoids have been identified as having strong antioxidant properties. Most interesting is the fact that, in addition to being one of the largest groups of antioxidant phytochemicals, flavonoids are also an integral part of the human diet as they are found in most fruits and vegetables. Cranberries are one of the most important sources of flavonoids that have a strong antioxidant and anti-inflammatory capacities. Thus, consumption of cranberries or their related products could be of importance not only in the maintenance of health but also in preventing CVD. The following review will present evidences supported for the most part by clinical observations that cranberries can exert potentially healthy effects for your heart.

Favourable impact of low-calorie cranberry juice consumption on plasma HDL-cholesterol concentrations in men

Posted
Authors
Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C
Journal
Br J Nutr 96(2):357-64
Abstract

A low HDL-cholesterol concentration is an independent risk factor for CVD. Studies have suggested that flavonoid consumption may be cardioprotective, and a favourable impact on circulating HDL-cholesterol concentrations has been suggested to partially explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on the plasma lipid profile of abdominally obese men. For that purpose, thirty men (mean age 51 (SD 10) years) consumed increasing doses of CJC during three successive periods of 4 weeks (125 ml/d, 250 ml/d, 500 ml/d). Before the study and after each phase, we measured changes in physical and metabolic variables. We noted a significant increase in plasma HDL-cholesterol concentration after the consumption of 250 ml CJC/d (+8.6+/-14.0% v. 0 ml CJC/d; P0.01), an effect that plateaued during the last phase of the study (500 ml CJC/d: +8.1+/-10.0% v. 0 ml CJC/d; P0.0001). Multivariate analyses revealed that changes in plasma apo A-I (R(2)=48%, P0.0001) and triacylglycerol (R(2)=16%, P0.005) concentrations were the only variables significantly contributing to the variation in plasma HDL-cholesterol concentration noted in response to the intervention. No variation was observed in total as well as in LDL and VLDL cholesterol. The present results show that daily CJC consumption is associated with an increase in plasma HDL-cholesterol concentrations in abdominally obese men. We hypothesise that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can be cardioprotective.

Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men.

Posted
Authors
Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C
Journal
Br J Nutr 99(2):352-9
Abstract

Elevated circulating concentrations of oxidized LDL (OxLDL) and cell adhesion molecules are considered to be relevant markers of oxidative stress and endothelial activation which are implicated in the development of CVD. On the other hand, it has been suggested that dietary flavonoid consumption may be cardioprotective through possible favourable impacts on LDL particle oxidation and endothelial activation. The present study was undertaken to determine the effect of the daily consumption of low-calorie cranberry juice cocktail on plasma OxLDL, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin concentrations in men. Thirty men (mean age 51 (sd 10) years) were recruited and asked to consume increasing daily doses of cranberry juice cocktail (125, 250 and 500 ml/d) over three successive periods of 4 weeks. Plasma OxLDL and adhesion molecule concentrations were measured by ELISA before and after each phase. We noted a significant decrease in plasma OxLDL concentrations following the intervention (P 0.0001). We also found that plasma ICAM-1 (P 0.0001) and VCAM-1 (P 0.05) concentrations decreased significantly during the course of the study. In summary, the present results show that daily cranberry juice cocktail consumption is associated with decreases in plasma OxLDL, ICAM-1 and VCAM-1 concentrations in men.

Antioxidant and antiproliferative activities of common fruits.

Posted
Authors
Sun J, Chu YF, Wu X, Liu RH
Journal
J Agric Food Chem 50(25):7449-54
Abstract

Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.

Plasma matrix metalloproteinase (MMP)-9 levels are reduced following low-calorie cranberry juice supplementation in men

Posted
Authors
Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B and Couillard C
Journal
J Am Coll Nutr 28(6):694-701
Abstract

OBJECTIVE: Matrix metalloproteinase (MMP)-9, also known as gelatinase B, is implicated in the development of hypertension and atherosclerotic plaque vulnerability to rupture, an important step in the etiology of cardiovascular diseases. Studies have suggested that flavonoid consumption may be cardioprotective, and its favorable impact on circulating MMP-9 concentrations could partly explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on plasma MMP-9 concentrations of abdominally obese men.
METHODS: Thirty men (mean age +/- SD: 51 +/- 10 years) consumed increasing doses of CJC during 3 successive periods of 4 weeks (weeks 1-4: 125 ml/day, weeks 5-8: 250 ml/day, and weeks 9-12: 500 ml/day). Before the study and after each phase, a series of physical and metabolic variables were measured, including MMP-9.
RESULTS: We found that CJC supplementation significantly decreased plasma MMP-9 concentrations (mean +/- SEM: -36% +/- 9%, p 0.0005; week 12 vs. baseline) while baseline plasma MMP-9 concentrations strongly correlated with the changes noted over the entire intervention (r = -0.71, p 0.0001). We also show that the reduction in plasma MMP-9 levels was associated with a change in plasma nitrites/nitrates (NOx) concentration over the entire intervention (r = -0.38, p 0.05; week 12 vs. baseline). Significant correlations were also noted between changes in plasma MMP-9 levels and those of systolic (r = 0.39, p 0.05) and diastolic (r = 0.60, p 0.001) blood pressure during the course of the study (week 12 vs. baseline).
CONCLUSIONS: Our results show that daily CJC consumption is associated with a decrease in plasma MMP-9 concentrations in abdominally obese men. We hypothesize that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can exert cardioprotective effects.

Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants.

Posted
Authors
Vinson JA, Bose P, Proch J, Al Kharrat H, Samman N
Journal
J Agric Food Chem 56(14):5884-91
Abstract

Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.

Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats.

Posted
Authors
Villarreal A, Stoecker BJ, Garcia C, Garcia K, Rios R, Gonzales C, Mandadi K, Faraji B, Patil BS, Deyhim F.
Journal
Phytomedicine 14(12):815-20
Abstract

BACKGROUND: We reported that drinking citrus juice improves bone quality in orchidectomized senescent male rats. Because cranberry juice, like citrus, is rich in nutrients and phenolic compounds, beneficial effects of citrus juice might also be seen with cranberry juice. An experiment evaluated effect of drinking cranberry juice on bone quality in orchidectomized rats.

METHODS: Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The treatments for the 4 months duration of the study were SHAM, orchidectomy (ORX), ORX+drinking either 27% or 45% cranberry juice concentrate added to drinking water. At the termination of the study, the rats were euthanized, blood was collected for plasma antioxidant status and IGF-I. The femur, tibia and the 4th lumbar were evaluated for bone quality. Total calcium and magnesium concentration in the femurs were also evaluated.

RESULTS: ORX did not affect red blood cell (RBC)-induced hemolysis despite lowering (p0.05) plasma antioxidant capacity; reduced (p0.05) plasma IGF-I, femoral density, femoral strength, time-induced femoral fracture, bone mineral content, bone mineral area; numerically (p=0.07) lowered 4th lumbar density; decreased (p0.05) trabecular connectivity, trabecular number, femoral ash; increased (p0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p0.05) plasma antioxidant status, protected RBC against hemolysis, but had no positive effect on bone quality or bone mineral status.

CONCLUSIONS: Cranberry juice increases plasma antioxidant status without affecting bone quality.

Cranberry juice increases antioxidant status without affecting cholesterol homeostasis in orchidectomized rats.

Posted
Authors
Deyhim F, Patil BS, Villarreal A, Lopez E, Garcia K, Rios R, Garcia C, Gonzales C, Mandadi K.
Journal
J Med Food 10(1):49-53
Abstract

Oxidative stress and hypogonadism are linked to the increased incidence of cardiovascular disease in males. The objective of this research was to delineate whether drinking cranberry juice for 4 months affects antioxidant capacity and lipid profile in orchidectomized rats. Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n = 8) and an orchidectomized group (n = 24). The orchidectomized group was divided into three groups of eight and assigned to one of the following treatments: orchidectomy, orchidectomy plus 27% cranberry juice, and orchidectomy plus 45% cranberry juice. At 120 days after initiation of the study, all rats were killed, blood was collected, and plasma was harvested for total antioxidant status, malondialdehyde, nitrate + nitrite, and superoxide dismutase (SOD) activity in liver, and concentrations of cholesterol and triglyceride in liver and in plasma. Orchidectomy depressed (P .05) plasma antioxidant capacity and SOD activity, elevated (P .05) nitrate + nitrite and malondialdehyde in plasma, and increased (P .05) triglyceride and cholesterol values in liver and in plasma. Cranberry juice increased (P .05) plasma antioxidant capacity and SOD activity and reduced (P .05) nitrate + nitrite and malondialdehyde concentrations. Drinking cranberry juice did not affect cholesterol concentrations in liver and in plasma. Triglyceride concentration in plasma of orchidectomized rats that were drinking cranberry juice increased (P .05), but its concentration in liver decreased (P .05) to the level of shams. The protective effect of cranberry juice from oxidative damage may be mediated by a decrease in nitrate + nitrite and dose-dependent decrease in peroxidation.

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Posted
Authors
Lee IT, Chan YC, Lin CW, Lee WJ, Sheu WH
Journal
Diabet Med 25(12):1473-7
Abstract

AIM: To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose-lowering drugs.

METHODS: Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 +/- 1 years) who were taking oral glucose-lowering medication regularly were enrolled in this randomized, placebo-controlled, double-blind study. Changes in lipid profiles, oxidized low-density lipoprotein (ox-LDL), glycaemic control, components of the metabolic syndrome, C-reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks.

RESULTS: Low-density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 +/- 0.2 to 2.9 +/- 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (-0.4 +/- 0.1 vs. 0.2 +/- 0.1 mmol/l, P 0.001). Total cholesterol and total : high-density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P 0.001 and P = 0.032, respectively). However, ox-LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups.

CONCLUSIONS: Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose-lowering agents.